In order to avoid the situation where two investigators study the same research question, please search our database to determine if your topic has already been studied. If you find that your topic or a related topic has already been submitted, you may wish to contact the investigator to inquire about his/her findings to determine how you might proceed. You may wish to collaborate or modify your request to avoid overlap. The results below reflect requests made since online requests have been accepted. As such, not all fields will have data as certain information, such as aims, were not collected until recently. If an entry has been assigned an ID # (e.g. DIAN-T1004), the full request has been submitted and is either approved, disapproved or in process.
Investigator: David Gate
Title: Spatial transcriptomics on vaccinated AD brains
Date of Request: September 18, 2023
Status: pending approval
ID: DIAN-T2309
Aim 1: Identify spatial transcriptomic changes associated with Aβ vaccination
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Investigator: Laurent Roybon
Title: Models and therapies for Alzheimer’s disease
Date of Request: August 16, 2023
Status: pending approval
ID: DIAN-T2308
Aim 1: Generate humanized models of early and advanced AD cellular pathogenesis
Aim 2: Use humanized models to explore a gene therapy for disease progression in AD
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Investigator: Sally Temple
Title: Assessing neurovascular interactions due to ADRD mutations
Date of Request: August 15, 2023
Status: pending approval
ID: DIAN-T2307
Aim 1: We will differentiate iPSCs with ADRD mutations versus controls into cerebral organoids and blood vessel cells. The goal is to examine the impact of the APP mutation on the organoids and blood vessel cells separately and interacting in a vascularized organoid.
Aim 2: The vascularized organoids will be sectioned and stained for Abeta, p-tau and the staining in different cell types will be quantified.
Aim 3: The conditioned medium produced by the vascularized organoids will be assessed for pathological markers and inflammatory factors.
Aim 4: The vascularized organoids will be dissociated for single cell -omics studies.
Investigator: Ji Yeun Hur
Title: Characterization of gamma-secretase complexes in fibroblasts and iPSCs from PS1 or PS2 FAD mutations
Date of Request: June 27, 2023
Status: pending approval
ID: DIAN-T2306
Aim 1: Characterize gamma-secretase complexes in fibroblasts and iPSCs
Aim 2: Characterize the gamma-secretase activity in fibroblasts and iPSCs
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Investigator: Bart De Strooper
Title: the role of presenilin mutation in microglia cell states
Date of Request: April 14, 2023
Status: approved
ID: DIAN-T2305
Aim 1: Profiling the gamma-secretase substrate proteome in PSEN1 H163R iPSC-derived microglia.
Aim 2: Characterizing the transcriptional and functional phenotype of human PSEN1 H163R microglia in a humanized chimeric AD mouse model.
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Investigator: Carlos Cruchaga
Title: Functional characterization of brain circular RNAs in Alzheimer disease using induced pluripotent stem cell models
Date of Request: April 4, 2023
Status: approved
ID: DIAN-T2304
Aim 1: To analyze the role of circHOMER1 in AD-related molecular phenotypes using cellular models
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Investigator: Eain Murphy (David Butler, Co-Invesitigator)
Title: Alzheimer’s Disease associated pathology induced by neurotropic viral infection.
Date of Request: March 3, 2023
Status: approved
ID: DIAN- T2303
Aim 1: Establish biomarkers and activity of SU110 and SU134 in iPSC-derived models of familial AD.
Aim 2: Do herpesvirus infections of neurons and glial cells produce neurodegenerative changes similar to those seen in Alzheimer’s Disease?
Aim 3: Assess the efficacy of anti-tau intrabodies to lower AD pathology in familial iPSC derived neurons with APP V717I iPSC mutation
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Investigator: Cruchaga
Title: Identification of mutation-specific networks: deep molecular profiling
Date of Request: February 13, 2023
Status: approved
ID: DIAN-T2302
Aim 1: Identification and Characterization of Cell-Specific Transposable Elements Implicated on Alzheimer Disease and Healthy Aging
Aim 2: To generate neuron and microglia specific ATAC-seq, CAGE-seq, DNA methylation and long-reads RNA-seq
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Investigator: Randall Bateman
Title: DIAN-TU-001 Gantenerumab Open Label Extension Study
Date of Request: January 27, 2023
Status: approved
ID: DIAN-T2301
Aim 1: The primary objective of the DIAN-TU-001 Gant OLE (3 years study duration) is to determine if continued treatment with Gant at a target dose of 1500 mg (subcutaneous administration, every 2 weeks) can result in continued or complete removal of brain amyloid plaque using cerebral amyloid imaging by PiB PET.
Aim 2: The key secondary objective of the OLE is to evaluate the efficacy of Gant in reducing disease progression and will be assessed for the following key secondary efficacy outcome measures, such as CSF and plasma biomarkers.
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Investigator: Nikolaos Robakis
Title: Effects of PS1 FAD mutants on brain angiogenesis.
Date of Request: October 17, 2022
Status: not approved
ID: DIAN-T2209
Aim 1: Examine whether VEGFR2 dimerization, VEGFR2/CTF1 peptide, VEGFR2 complexes, VE-cadherin angiogenic complexes and levels of VEGF ligand differ in human FAD brains compared to control brains.
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Investigator: Ralph A. Nixon
Title: PSEN FAD mutation effects on autophagy-lysosomal pathway related gene regulation
Date of Request: September 12, 2022
Status: approved
ID: DIAN-T2208
Aim 1: Transcriptomic analysis of PSEN1 FAD mutations
Aim 2: Transcriptomic analysis of PSEN2 FAD mutations
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Investigator: Henderson
Title: Stanford Alzheimer’s Disease Research CenterAdmin Supp: Developing iPSC modelsfor AD and PD
Date of Request: September 2, 2022
Status: approved
ID: DIAN-T2207
Aim 1: AD/ADRD phenotypic characterization of iPSC neurons and microglia. Aim 2.1: We will differentiate and characterize cell lines into cortical neurons and microglia using established and validated protocols. Aim 2.2: We will characterize cell cultures and media supernatant for established AD biomarkers, including total tau, phosphorylated tau (Thr181), A1-40, and A1-42, neurofilament light (NfL), alpha-synuclein, cytokines and chemokines, immune profiling with CYTOF, proteomics, and comparative analyses to cerebrospinal fluid (CSF) biomarkers from the same donor.
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Investigator: Pharma partner
Title: Comprehensive analyses of the soluble microtubule binding region (MTBR) in Alzheimer disease progression
Date of Request: August 17, 2022
Status: approved
ID: DIAN-T2206
Aim 1: To test the performance of a pharma partner’s antibody to identify unique soluble tau MTBR epitopes
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Investigator: Tammie Benzinger
Title: Quantification of Neuroinflammation in Autosomal Dominant Alzheimer’s Disease Using Small-block Brain Specimen imaged by Diffusion Basis Spectrum Imaging (DBSI)
Date of Request: August 16, 2022
Status: withdrawn
ID: DIAN-T2205
Aim 1: to assess the value of DBSI for the study of ADAD by comparing post-mortem MRI signals with histologic data
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Investigator: Patrick Oeckl
Title: Investigation of plasma Beta-Synuclein levels in asymptomatic and symptomatic autosomal dominant Alzheimer´s disease
Date of Request: June 20, 2022
Status: approved
ID: DIAN-T2204
Aim 1: To investigate if blood levels of the synaptic marker Beta-Synuclein are already elevated in asymptomatic ADAD
Aim 2: To estimate a time course of blood Beta-Synuclein changes in ADAD based on EYO and comparison with other blood/CSF biomarkers
Aim 3: Relationship of blood Beta-Synuclein levels in ADAD with other fluid and imaging biomarkers, brain atrophy and cognitive impairment
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Investigator: Antonio Boza Serrano
Title: Galectin-3 as a prognostic biomarker to monitor Autosomal dominant Alzheimer’s Disease’s progression
Date of Request: April 27, 2022
Status: not approved
ID: DIAN-T2202
Aim 1: We aim to evaluate if gal3 levels are elevated in ADAD and if they might track the progression of AD pathology.
Aim 2: We want to compare the levels of gal3 with the levels of the classic biomarkers (amyloid-beta 42, total tau, p-tau (181, 217, etc), neurofilaments, precuneus SURV and PIB-Pet) as well as with global cognitive test (MMSE) and clinical measures (CDR total and SB) scores from the DIAN-obs
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Investigator: Giuseppina Tesco
Title: Study of endolysosomal alterations (including exosomes) in brain cells cultures derived from fDA iPSC lines and isogenic controls
Date of Request: January 25, 2022
Status: approved
ID: DIAN-T2201
Aim 1: Determine the effect of mutant APP on exosome dynamics in CNS cells in human AD models.
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Investigator: Jee Hoon Roh/Jae-Hong Lee
Title: Epigenetic analyses to assess the resilience among DIAN mutation carriers
Date of Request: December 15, 2021
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Aim 1: To investigate the potential epigenetic causes of resilience among DIAN mutation carriers who are discordant in disease courses measured by biomarkers.
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Investigator: Cruchaga
Title: Multi-Omics CSF and plasma signature of ADAD
Date of Request: October 16, 2021
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Aim 1: To identify ADAD-specific multi-omic (proteomics and metabolomic) signatures CSF and plasma
Aim 2: To identify multi-omic (metabolomics and proteomics) plasma signatures and QTLs in ADAD
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Investigator: Dan Nicholson
Title: High-resolution multiplex localization of Alzheimer’s disease risk and resilience factors
Date of Request: September 23, 2021
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ID:
Aim 1: Determine the expression levels, localization, and co-localization patterns of proteins in the m109 and BIN1 protein clusters in relation to synaptic markers. Synaptic changes have long been recognized to be tightly linked to AD severity (9). We will determine the expression patterns of the two protein clusters relative to excitatory and inhibitory synapses using antibodies specific for excitatory synapses (e.g., AMPA- and NMDA-type receptors and PSD-95), inhibitory synapses (e.g., vesicular GABA transporter/VGAT and gephyrin), and presynaptic terminals (e.g., synapsin).
Aim 2: Determine the expression levels, localization, and co-localization patterns of proteins in the m109 and BIN1 protein clusters in relation to AD pathology. Probable AD is confirmed at autopsy by the presence of amyloid plaques and tangles (10). We will determine the expression patterns of the two protein clusters as a function of proximity to regions with amyloid plaques (using a 6E10 antibody), neurofibrillary tangles (using a tau13 antibody), astrocytes (using a GFAP antibody), and microglia (using an Iba1 antibody).
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Investigator: Ronald Davis
Title: Capturing the mitochondrial complexity in familial Alzheimer’s disease
Date of Request: September 15, 2021
Status: pending
ID: DIAN-T2107
Aim 1: Use high-content and high-throughput assays to quantify the MT dynamics phenotypes that develop in neurons derived from iPSCs of fAD subjects compared to age-matched and/or isogenic controls.
Aim 2: Define the functional impairment in these neurons (IMM-inner mitochondrial membrane potential).
Aim 3: Interrogate the function of the electron transport chain (ETC) in these neurons.
Aim 4: Measure the structural integrity of MT, the ETC, and MT-related processes in these neurons by quantitative Western blotting of proteins
Investigator: Randall J Bateman
Title: Comprehensive analyses of the soluble microtubule binding region (MTBR)in Alzheimer disease progression.
Date of Request: September 2, 2021
Status: approved
ID: DIAN-T2106
Aim 1: The Primary Aim of this study isto identify which tau species are novel and different inthe novelUCB vs. other antibodies which have been used to characterize the soluble tau in CSF of DIAN(e.g. Tau1 or E2814).
Aim 2: The stage of the disease where additional MTBRisoforms begin to differ between MC and NC based on EYO and Aβ status andcompare this to the recently identified MTBR and p-tau mass spec measures of MTBR tau and p-tau.
Aim 3: The longitudinal change (quantitative change / mean and SD) of thenovel MTBRfragmentsas it relates to disease stage and how this compares to the recently identified MTBR and p-tau mass specmeasures of MTBR tau and p-tau.
Aim 4: The association between regional NFT tau burden (post-mortem) and MTBR (based on the novel antibody and Eisai antibody) to assess for the correlation between soluble and insoluble fractions of MTBR with AD related NFTs. Design:
Investigator: Mariah S. Hahn
Title: Targeting Dysregulated Synapse and Proteostasis Mechanisms in Alzheimer’s Disease
Date of Request: June 3, 2021
Status: approved
ID: DIAN-T2105
Aim 1: Develop a 3D culture system compatible with long-term (>3 month) iNeuron culture, extension, synapse formation and elimination, and quantitative assessment of neural circuit activity using “healthy” networks.
Aim 2: Compare AD_(PSEN1)-iNeuron cultures to iNeuron cultures derived from unaffected family member controls with respect to Aβ, tau phosphorylation, synapse maintenance and proteostasis.
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Investigator: Johannes Levin
Title: Molecular detection of α-synuclein co-pathology in ADAD mutation carriers
Date of Request: April 29, 2021
Status: approved
ID: DIAN-T2104
Aim 1: Use real time quaking induced conversion (RT-QuIC) for ante mortem detection of Synuclein pathology in ADAD mutation carriers
Aim 2: Compare the data from RT-QuIC regarding in vivo detection of Synuclein pathology with data from post mortem examinations (manuscript in preparation).
Aim 3: Within the time frame of 15 years EYO we will analyse the time-point of emergence of LB pathology as measured by RT-QuIC .
Aim 4: We will analyse clinical and imaging data longitudinally comparing RT-QuIC positive and RT-QuIC negative participants.
Investigator: Rawan Tarawneh
Title: VE-cadherin in Alzheimer Disease
Date of Request: April 4, 2021
Status: not approved
ID: DIAN-T2103
Aim 1: Examine the diagnostic value of CSF and plasma levels of VE-cadherin as a marker of vascular injury in EOAD
Aim 2: Investigate whether VE-cadherin correlates with CSF and imaging measures of amyloid, tau, brain atrophy, and glucose hypometabolism in EOAD in cross-sectional and longitudinal analyses
Aim 3: Determine whether baseline VE-cadherin levels influences age of onset or rate of cognitive decline in asymptomatic and symptomatic mutation carriers
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Investigator: Charlotte Teunissen
Title: Measurement of glial fibrillary acidic protein (GFAP) levels in blood for evaluation of astrocyte reaction in Alzheimer disease.
Date of Request: August 14, 2020
Status: approved
ID: DIAN-T2010
Aim 1: Determine trajectory of GFAP over the ADAD disease course in relation to amyloid
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Investigator: Teunissen
Title: Add-on DIAN project 3 Novel mechanisms: pilot OLINK proteomics in left-over CSF aliquots
Date of Request: August 14, 2020
Status: not approved
ID: DIAN-T2009
Aim 1: Study which OLINK proteins (signature) are discriminative between ADAD and controls
Aim 2: Compare with sporadi AD
Aim 3: Compare with Mass Spec in ADAD
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Investigator: Oscar Harari
Title: Metabolomic and lipidomics changes in ADAD
Date of Request: August 13, 2020
Status: approved
ID: DIAN-T2011
Aim 1: Determine metabolite signatures of ADAD
Aim 2: Identify locus-metabolite and lipids associations via Metabolite genome-wide association studies (M-GWAS).
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Investigator: Ronald Hawley
Title: TEST BIO SUBMISSION
Date of Request: August 7, 2020
Status:
ID:
Aim 1: test the form
Aim 2: test the form 2
Aim 3: test the form 3
Aim 4: test the form 4
Investigator: Laura Ibanez
Title: Plasma cell-free RNA as non-invasive biomarker for neurodegeneration
Date of Request: August 5, 2020
Status: not approved
ID: DIAN-T2007
Aim 1: Validate genomic models for disease pathology in Autosomal Dominant Alzheimer
Aim 2: Develop a specific predictive model for ADAD
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Investigator: Randall Bateman
Title: Identification and validation of novel AD biomarkers for clinical development of Eisai AD pipelines
Date of Request: July 2, 2020
Status: withdrawn
ID: DIAN-T2006
Aim 1: To profile of CSF MTBR-tau isoforms which can be captured by E2814 across all DIAD stages using CSF samples from DIAN-observation cohort.
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Investigator: 1) Dr. Alison M. Goate, 2) Dr. Sarah M. Neuner
Title: Defining the role of microglia in Alzheimer’s disease risk and resilience
Date of Request: April 1, 2020
Status: approved
ID: DIAN-T2005
Aim 1: Aim 1: Investigate the effect of high-risk or protective amyloid precursor protein (APP) mutations on microglia cell function.
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Investigator: Jérôme Braudeau
Title: Optimization of a blood diagnosis of the silent phase of Alzheimer’s disease
Date of Request: March 11, 2020
Status: not approved
ID: DIAN-T2004
Aim 1: Confirm the performance of a diagnostic algorithm developed on European plasma samples.
Aim 2: Improve the algorithm by learning on human plasma samples of more varied genetic origin and environmental background.
Aim 3: Improve the algorithm by learning on human plasma samples collected longer before the diagnosis of Alzheimer’s disease.
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Investigator: Henrietta Nielsen
Title: Apolipoprotein E isoform levels and their relevance to the development of AD pathology
Date of Request: March 11, 2020
Status: not approved
ID: DIAN-T2003
Aim 1: By use of mass-spectrometry assess and compare the individual apolipoprotein E isoform levels in plasma and CSF from familial AD patients versus controls
Aim 2: To investigate whether fluid levels of apolipoprotein E are related to the estimated year of disease onset, CSF and imaging AD biomarkers in familial AD patients
Aim 3: To elucidate a potential correlation between plasma apolipoprotein E levels and previously assessed CSF alpha-synuclein levels whereof the latter appeared related to amyloid-beta deposition and symptom onset
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Investigator: Zlokovic, Berislav V. and Toga, Arthur W.
Title: Blood-brain barrier dysfunction in autosomal dominant Alzheimer’s disease (ADAD)
Date of Request: February 9, 2020
Status: approved
ID: DIAN-T2001
Aim 1: To evaluate the effects of ADAD mutations on the molecular biomarkers of NVU and BBB dysfunction in PSEN1 and other ADAD pre-symptomatic and symptomatic MCs compared to non-MC carriers, and determine how they relate to each other, and whether NVU/BBB dysfunction can contribute to cognitive impairment and other pathologies in ADAD.
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Investigator: Jihwan Song
Title: Comparison of the iPSC Characteristics between Caucasian and Asian ADAD Families
Date of Request: December 10, 2019
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ID: DIAN-T1916
Aim 1: To compare charateristics of iPSCs between caucasian and asian ADAD families
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Investigator: Dennis Selkoe
Title: Plasma Levels of an N-terminal Tau Fragment as Predictors of Cognitive Decline and Neurodegeneration in DIAN
Date of Request: December 10, 2019
Status: approved
ID: DIAN-T1915
Aim 1: Using cross-sectional and longitudinal plasma samples from DIAN, we will assess levels of plasma NT1 (SIMOA) and correlate these with estimated years to symptom onset (EYO), rates of neurodegeneration (MRI-based), and cognitive performance (using the DIAN global cognitive composite).
Aim 2: Using pre-existing measures of NfL from prior DIAN studies, we will compare and contrast the associations of plasma NfL and NT1 to cognitive and neurodegenerative trajectories.
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Investigator: Oscar Harari
Title: Brain DNA methylation in Autosomal Dominant Alzheimer’s disease
Date of Request: October 29, 2019
Status: approved
ID: DIAN-T1914
Aim 1: Aim 1: To identify Differentially Methylated Loci (DML) in ADAD and sporadic AD and neuropath-free controls
Aim 2: Aim 2. To identify genetic loci modulating DML, and their downstream impact in brain transcriptomic/proteomic profiles.
Aim 3: Aim 3. To evaluate the causal relationship between DML and AD pathogenesis.
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Investigator: Randall Bateman
Title: Fluid NfL levels to be used as control and run-in data for the DIAN TU
Date of Request: October 18, 2019
Status: withdrawn
ID: DIAN-T1913
Aim 1: To measure NfL levels in CSF and matched plasma smaples for use as control and run-in data in the DIAN TU
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Investigator: Carlos Cruchaga
Title: Genomic-based biomarkers for Alzheimer’s Disease
Date of Request: October 17, 2019
Status: withdrawn
ID: DIAN-T1912
Aim 1: Aim 1: To construct prediction models for AD using cell-free nucleic species.
Aim 2: Aim 2: To create novel prediction models using circular RNAs as biomarkers
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Investigator: N/A
Title: Therapeutic development for familial Alzheimer’s disease
Date of Request: September 29, 2019
Status: approved
ID: DIAN-T1910
Aim 1: To determine whether therapeutic candidates can affect Abeta processing in cultured fibroblasts from autosomal dominant Alzheimer disease (ADAD) patients with PSEN1 mutations
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Investigator: N/A
Title: Gene therapy for familial Alzheimer’s disease
Date of Request: September 29, 2019
Status: approved
ID: DIAN-T1910
Aim 1: To determine whether introduction of wildtype PS1 can rescue γ-secretase activity in cultured fibroblasts from autosomal dominant Alzheimer disease (ADAD) patients with PSEN1 mutations
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Investigator: Kaj Blennow
Title: Truncated tau species tau224 and tau368 in CSF and P-tau181 in plasma in familial AD as indicators of pathological brain tau metabolism
Date of Request: August 14, 2019
Status: withdrawn
ID: DIAN-T1908
Aim 1: To examine how novel CSF biomarkers for tau pathology (tau truncated at positions 224 or 368) change with onset of amyloid pathology and tau pathology, as well as clinical disease onset and progression in familial AD
Aim 2: To examine how plasma P-tau181 changes with onset of amyloid pathology and tau pathology, as well as clinical disease onset and progression in familial AD
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Investigator: Catherine Marquer
Title: SYNAPTOJANIN 1 LEVELS IN DOMINANTLY INHERITED ALZHEIMER’S DISEASE
Date of Request: July 5, 2019
Status: approved
ID: DIAN-T1907
Aim 1: To test whether the protein levels of Synaptojanin1 are increased in dominantly inherited Alzheimer’s disease (DIAD), as they are in sporadic and Down Syndrome-AD
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Investigator: Djamel Lebeche
Title: Pharmacological Validation of SERCA Activators for Diabetes Associated ADRD
Date of Request: May 12, 2019
Status: approved
ID: DIAN-T1906
Aim 1: To test SERCA activators in in vitro assays to assess their ability to rescue neuronal cells from ER stress-induced cell death (neuroprotection)
Aim 2: To test the effects of SERCA activators in animal model of diabetes and Alzheimer’s disease (APP/PS1-Ob/ob mice), and in iPSC derived from AD patients
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Investigator: Houlden and Kullmann/Houlden
Title: Dominant and Recessive Intronic Repeat Expansions in Neurodegeneration
Date of Request: February 25, 2019
Status: Withdrawn
ID: DIAN-T1903
Aim 1: Screen for the GGC repeat expansion in the NOTCH2NLC gene recently associated with dominant or sporadic neurodegeneration from our and Japanese labs.
Aim 2: Screen the AAGGG recessive expansion seen in the RF gene associated with ataxia, MSA-like phenotype and neurodegeneration.
Aim 3: We will haplotype patients with expansions to understand relationships between samples, SNPs associated with the disease and possible founder effects.
Aim 4: Feedback results to be paired with biobank samples
Investigator: na
Title: RIPK1 regulated metabolic biomarkers
Date of Request: February 14, 2019
Status: Not approved
ID: DIAN-T1902
Aim 1: Compare the baseline distribution of RIPK1 regulated metabolic biomarkers in CSF samples from DIAN patients vs. cognitively normal non-carrier family member controls
Aim 2: Generate biomarker hypothesis to inform the decision making for a DIAN population in phase2a clinical trial with RIPK1 inhibitors
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Investigator: Steven M. Greenberg
Title: CSF Biomarkers for Dutch-type Hereditary Cerebral Amyloid Angiopathy
Date of Request: February 7, 2019
Status: approved
ID: DIAN-T1901
Aim 1: 1. Perform multiplex immunoassay measurements of a range of candidate biomarkers in cerebrospinal fluid (CSF) samples from carriers and non-carriers of the Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) mutation enrolled in DIAN.
Aim 2: 2. Perform parallel immunoassays on plasma samples drawn at similar timepoints to determine the correlation between CSF and plasma concentrations.
Aim 3: 3. Correlate CSF and plasma biomarkers with neuroimaging, biochemical and clinical features in the enrolled mutation carriers.
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Investigator: Suman Jayadev
Title: Immune Cell Pathways in ADAD
Date of Request: December 10, 2018
Status: No Request Made
ID: NA
Aim 1: To identify innate immune cell phenotypes and gene regulatory networks in familial AD. Innate immune genes and loci harboring immune genes have been associated with sporadic AD though less is known about cell type specific immune gene networks in familial AD. Evidence from studies including those from DIAN investigators have demonstrated early changes in microglial proteins, in mutation carriers prior to clinical onset of disease. This suggests that microglial or innate immune cell activity, be it loss of homeostatic function, activation of inflammatory or tissue repair responses, disease associated responses or other yet to be defined phenotypes may contribute to FAD progression and serve as a potential therapeutic target in combination with other therapies. While modulating immune pathways in FAD may be a viable intervention, a clearer understanding of the disease relevant drivers of neural and peripheral immune pathways are needed for appropriate targeting. We propose to evaluate transcriptomic data from single nuclei and microglial enriched nuclei, isolated from frozen cortical tissue (parietal or frontal – depending upon tissue availability) from 20 FAD carriers and establish gene expression modules annotated by neural cell type. These data will be analyzed in comparison to 20 sporadic AD and 10 pathology negative controls (funding pending for sporadic AD cases). Further computational approaches by collaborators at SAGE Bionetworks will be pursued to identify proximal molecular networks in microglial, neuronal, and other glial cell types that are both shared and distinct between FAD and SAD. Additionally, we will determine the relative representation of immune cell populations and diversity of phenotypes. These studies aim to highlight the networks mediating glial biology associated with FAD. In addition, identification of the molecular programs which are shared or distinct between FAD and SAD will be relevant for therapeutic design and disease modeling for both forms of disease.
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Investigator: Not funded
Title: The Role of TRIC chaperonin in AD pathogenesis
Date of Request: September 14, 2018
Status: approved
ID: DIAN- T1905
Aim 1: To test the hypothesis that TRIC chaperonin repression occurs in neuronal differentiated AD IPSC compared to WT IPSC.
Aim 2: To test the hypothesis that autophagy dysfunction occurs in neuronal differentiated AD IPSC compared to WT IPSC.
Aim 3: To test the hypothesis that manipulation of the TRIC chaperonin can alter autophagy function of neuronal differentiated AD IPSC.
Aim 4: To test the hypothesis that manipulation of the TRIC chaperonin alters AB levels in neuronal differentiated AD IPSC.
Investigator: Erik Johnson, Allan Levey
Title: A Proteomic Network Comparison of Autosomal Dominant and Sporadic Alzheimer’s Disease
Date of Request: August 13, 2018
Status: Approved
ID: DIAN-T1805
Aim 1: Compare the brain protein network alterations that characterize autosomal dominant AD with those observed in sporadic early-onset AD
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Investigator: Xiongwei zhu
Title: Mitochondrial deficits in AD patient iPSC-derived neurons
Date of Request: July 26, 2018
Status:
ID: DIAN-D1804
Aim 1: Investigate abnormalities in mitochondrial dynamics and quality control in patient iPSC-derived human neurons
Aim 2: Investigate molecular mechanism underlying mitochondrial dynamic and quality control abnormalities in patient iPSC-derived human neurons
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Investigator: Guojun Bu
Title: Mechanistic and functional assessment of sporadic early-onset AD
Date of Request: July 4, 2018
Status: Pending
ID: DIAN-T1803
Aim 1: Investigate amyloid-related mechanisms of familial and sporadic EOAD patient-derived fibroblasts, patient iPSC-derived neurons and directly converted neurons
Aim 2: Assess the function, structure and potential pathological pathways of sporadic EOAD, familial EOAD, healthy and LOAD patient-derived iPSC-derived neurons and directly converted neurons
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Investigator: Dr. Tammie Benzinger
Title: Imaging Tauopathy in the Dominantly Inherited Alzheimer Network (DIAN)
Date of Request: February 15, 2018
Status: Pending
ID: DIAN-T1802
Aim 1: Aim 1: To study the temporal dynamics of tau deposition (using AV-1451). This proposal studies tauopathy in relation to existing biomarkers within DIAN participants including: CSF (CSF tau, p-tau, Aβ42), neuroimaging [Aβ PET and structural and functional magnetic resonance imaging (MRI)], and cognitive performance [clinical dementia rating sum of boxes (CDR-SB) and neuropsychometric testing]. We will relate AV1451 uptake to EYO to determine timing of tau changes relative to conversion to symptomatic AD. Hypothesis: PET tau changes occur after Aβ (CSF Aβ42 and PET Aβ) and after soluble CSF tau but before MRI (structural or functional) or neuropsychometric changes in DIAN.
Aim 2: Aim 2: To study the spatial (both local and distributed) changes of tau deposition (using AV-1451). We will examine the spread of tauopathy along structural and functional connections. We will identify the spatial pattern of tauopathy during the crucial transition from preclinical to symptomatic AD. Additionally, using novel mathematical models, we will correlate the topography of tau PET with both cross-sectional and longitudinal spatial patterns seen with other imaging biomarkers (Aβ PET and MRI [structural and functional]). Hypothesis: Phenoconversion from cognitively normal to symptomatic dementia is associated with neocortical tau deposition. The spread of tau deposition is predicted by functional/structural connections.
Aim 3: Aim 3 (exploratory): Study the relationship between in vivo tau deposition and neuropathology. We will perform quantitative measures of cortical tauopathy NFT, NP, and neuropil thread (NT) burden in twenty-five brain areas using tau-immunostained sections and automated stereological methods. We will perform quantitative autoradiography with [3H]AV-1451 in the same tissue samples to validate receptor binding specificity and quantify tauopathy. Neuropathological results will be aligned with in vivo imaging using an ex vivo MRI prior to sectioning. Hypothesis: There will be a strong correlation between tau burden as assessed by AV-1451 in vivo imaging, [3H]AV-1451 autoradiography, and anti-tau antibodies.
Aim 4:
Investigator: Nigel Hooper
Title: Development of blood-based proteomic biomarkers of Alzheimer’s disease
Date of Request: February 15, 2018
Status: Pending
ID: DIAN-T1801
Aim 1: Our study aims to identify a blood-based biomarker panel using SWATH-MS that can detect AD at an early asymptomatic stage
Aim 2:
Aim 3:
Aim 4:
Investigator: CHRISTIAN HAASS
Title: Longitudinal changes of the microglia activity markers sTREM2 and Progranulin in CSF of Dominantly Inherited Alzheimer’s disease
Date of Request: December 12, 2017
Status: Pending
ID: DIAN-T1712
Aim 1: To determine longitudinal changes in CSF sTREM2 and CSF PGRN levels across the range of EYO.
Aim 2: To determine the association between baseline levels of CSF sTREM2 and CSF PGRN and their rate of change with longitudinal cognition, brain structure and metabolism at different stages of ADAD
Aim 3: Assess the cross-sectional association between CSF sTREM2 or CSF PGRN and AV1451 PET across different EYO.
Aim 4:
Investigator: Florin Despa
Title: Role of amylin in AD
Date of Request: November 27, 2017
Status: Pending
ID: DIAN-T1711
Aim 1: Test the hypothesis that the ratio of serum amylin to CSF amylin levels increases in fAD compared to age-matched cognitively normal individuals.
Aim 2: Test the hypothesis that amylin interacts with Abeta to form mixed amylin-Abeta oligomers within CSF and serum in patients with fAD. We propose to measure the levels of mixed Abeta-amylin oligomers within CSF and serum in patients with fAD versus age-matched cognitively normal individuals.
Aim 3:
Aim 4:
Investigator: Carlos Cruchaga
Title: Identification of mutation-specific networks. Amended
Date of Request: November 2, 2017
Status: Pending
ID: DIAN-T1710
Aim 1: To generate RNA-seq data from brain tissue from DIAN participants (mutation carriers and non-carriers)
Aim 2: To identify genes differentially expressed or spliced in mutation carriers vs LOAD, and vs controls
Aim 3: To identify gene and mutation-specific networks and pathways
Aim 4:
Investigator: Mikael Simons
Title: Lipidomics study of preclinical plasma biomarkers for Alzheimer´s disease
Date of Request: October 11, 2017
Status: Pending
ID: DIAN T1709
Aim 1: Establish a preclinical biomarker for AD
Aim 2: Determine lipid profiles in preclinical AD
Aim 3: Compare lipid profiles in DIAN and Framingham
Aim 4: Determine longitudinal changes of lipid profiles during disease
Investigator: Laurent Roybon
Title: AD pathology in advanced cellular models
Date of Request: September 10, 2017
Status: Pending review
ID: DIAN-T1708
Aim 1: Generation of iPSCs from AD patient fibroblasts
Aim 2: Differentiation of AD iPSCs into neurons
Aim 3: Analysis of cellular networks dysfunction
Aim 4:
Investigator: Makoto Ishii
Title: Leptin and metabolic signaling in autosomal dominant Alzheimer’s disease
Date of Request: September 7, 2017
Status: Pending review
ID: DIAN-T1707
Aim 1: To determine if alterations in levels of plasma leptin and related metabolic markers are evident in cognitively normal subjects with autosomal dominant Alzheimer’s disease
Aim 2: To determine if alterations in plasma leptin levels and related metabolic markers correlate with changes in Alzheimer’s disease biomarkers in subjects with autosomal dominant Alzheimer’s disease
Aim 3: To determine if levels of plasma leptin and related metabolic markers correlate with worsening Alzheimer’s disease biomarkers and progression of cognitive decline over time (age) in subjects with autosomal dominant Alzheimer’s disease
Aim 4:
Investigator: Steve Wagner, Ph.D.
Title: Preclinical validation of target engagement for a potent disease modifying therapeutic for AD in dominantly inherited EOFAD patient induced human neurons
Date of Request: August 16, 2017
Status:
ID: DIAN-T1706
Aim 1: Demonstrate target engagement against human neurons harboring EOFAD mutations
Aim 2: Evaluation of the effects of GSMs in hiPSC in-vitro systems on downstream AD pathways
Aim 3:
Aim 4:
Investigator: Eric McDade
Title: Comprehensive CSF tau profiling in DIAN using a novel mass spectrometry
Date of Request: May 10, 2017
Status:
ID: DIAN-T1705
Aim 1: Determine stage of the disease where additional p-tau isoforms (particularly p-tau Thr 217) begin to differ between MC and NC based on EYO and Aβ status, and compare this to the currently used immunoassay measures of tau and p-tau181.
Aim 2: Determine longitudinal change (quantitative change / mean and SD) of the various p-tau isoforms identified as it relates to disease stage and how this compares to the currently used immunoassay measures of tau and p-tau181.
Aim 3: Assess the association between baseline and longitudinal CSF MS p-tau isoforms and other measures of disease (neuroimaging- FDG �PET, MRI volumetrics and tau �PET; clinical- CDR, cognition).
Aim 4: Compare the comprehensive CSF tau profile identified in DIAN with that completed and underway in sAD at Washington University by Drs. Barth�lemy and Bateman.
Investigator: Alison Goate
Title: Characterization of γ-Secretase in fibroblasts derived from FAD patients harboring PSEN1or PSEN2 mutations
Date of Request: March 9, 2017
Status:
ID: DIAN-T1704
Aim 1: Determine in vitro γ-secretase activity for Aβ40 and Aβ42 production using fibroblast cell membranes
Aim 2: Characterize the γ-secretase complexes in fibroblast cell membranes
Aim 3: Examine the sensitivity of various modulators and inhibitors to γ-secretase in fibroblast cell membranes
Aim 4:
Investigator: Cruchaga
Title: Genetic architecture of CSF biomarker levels in ADAD
Date of Request: February 27, 2017
Status:
ID: DIAN-T1702
Aim 1: To identify genetic variants and genes associated with CSF biomaker levels in DIAN
Aim 2: To determine the overlap in the genetic architecture of late-onset sporadic AD with ADAD
Aim 3: To identify protective and modifiers variants for AD
Aim 4:
Investigator: Randall Bateman
Title: DIAN-ADNI comparison study
Date of Request: February 23, 2017
Status:
ID: DIAN-T1703
Aim 1: In LOAD and ADAD determine whether both groups demonstrate initial cerebral amyloidosis that is followed by the development of neurodegeneration prior to onset of AD symptoms
Aim 2: Characterize similarities and any differences in AD phenotypes between LOAD and ADAD
Aim 3: In both LOAD and ADAD, determine whether there is a pattern of disease progression that is marked by intra-individual global cognitive and functional decline that culminates in death
Aim 4: Examine the contribution of age to the dementing process.
Investigator: Young-Pearse
Title: Investigating Cell-type dependent phenotypes in familial Alzheimer’s disease
Date of Request: December 27, 2016
Status:
ID: DIAN-T1701
Aim 1: To determine if there are differential effects of neuronal subtype on APP processing with fAD mutation
Aim 2: To determine if there are differential effects of neuronal subtype on tau proteostasis with fAD mutation
Aim 3:
Aim 4:
Investigator: Jacques P. Tremblay
Title: Development of a treatment of Alzheimer based on the editing of the Amyloid Precuror Protein gene with the CRISPR system
Date of Request: October 24, 2016
Status:
ID: DIAN-T1613
Aim 1: To correct the APP gene in 293T cells and in Alzheimer cells with a pair of gRNA (targeting sequences in intron 15 or 16) and with dCas9-FokI
Aim 2:
Aim 3:
Aim 4:
Investigator: MPIs: Tom Montine and Mike MacCoss
Title: Molecular Phenotyping in Alzheimer’s Disease
Date of Request: October 21, 2016
Status:
ID: DIAN-T1612
Aim 1: We will collect proteomics data on post-mortem brain samples using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategy called data independent acquisition.
Aim 2: Leverage high-dimensional proteomics data to identify and understand the molecular signatures of three groups that will enable precision medicine for AD: (i) different genetic risk, (ii) common co-morbidities, and (iii) resilience to AD neuropathologic change.
Aim 3: We will make our data available through a novel cloud based solution, called the Chorus Project (http://chorusproject.org), engineered to enable big data reanalysis by the community of scientists.
Aim 4:
Investigator: Hideyuki Okano
Title: In-depth characterization of iPSC-derived neuronal models carrying familial dementia mutations
Date of Request: September 30, 2016
Status:
ID: DIAN-T1611
Aim 1: Generation and development of human neuronal models with dementia-related dysfunctions
Aim 2: To explore molecular mechanism of neuronal malfunctions by FAD-linked mutations
Aim 3:
Aim 4:
Investigator: Dr. A Claudio Cuello
Title: Investigating early NGF dysmetabolism as a source of novel biomarkers in ?silent? stages of Alzheimer?s disease
Date of Request: September 23, 2016
Status:
ID: DIAN-T1610
Aim 1: To investigate plasma markers of NGF dysmetabolism as a source of biomarkers in pre-clinical AD
Aim 2: To investigate CSF markers of NGF dysmetabolism as a source of biomarkers in pre-clinical AD
Aim 3:
Aim 4:
Investigator: Alice PEBAY
Title: Human iPSC-derived organoids to study Alzheimer?s disease
Date of Request: September 9, 2016
Status:
ID: DIAN-T1609
Aim 1: to generate cortical organoids from iPSCs of AD patients and controls
Aim 2: to generate iPSCs from APP mutation fibroblasts
Aim 3: To study pathological events of AD in organoids
Aim 4:
Investigator: Sidney Strickland
Title: Aβ-specific fibrin fragment resistant to fibrinolysis in the CSF and plasma of familial AD patients with HCHWA
Date of Request: September 7, 2016
Status:
ID: DIAN-T1608
Aim 1: Analyze the level of fibrin degradation products in the antemortem CSF of HCHWA patients and compare levels to sporadic AD cases and non-demented controls.
Aim 2: Analyze the level of an A?-specific fibrin fragment resistant to fibrinolysis in the plasma of AD patients with HCHWA and compare levels to sporadic AD cases and non-demented controls.
Aim 3:
Aim 4:
Investigator: Randall Bateman
Title: DIAN-ADNI Comparison study
Date of Request: July 19, 2016
Status:
ID: DIAN-T1607
Aim 1: characterize the stages of preclinical AD with amyloid PET and cerebrospinal fluid (CSF) concentrations of Aβ and tau and phosphorylated tau (p-tau) and determine whether both groups demonstrate initial cerebral amyloidosis that is followed by the development of neurodegeneration prior to onset of A
Aim 2: In both ADAD and LOAD, determine whether initial symptoms of AD are characterized by subjective reports (self-reported and those of a study partner) of the gradual onset of memory impairment as well as by deficits in objective measures of episodic memory
Aim 3: In both LOAD and ADAD, determine whether there is a pattern of disease progression that is marked by intra-individual global cognitive and functional decline that culminates in death.
Aim 4: Characterize other similarities and any differences in AD phenotypes between LOAD and ADAD
Investigator: Mathias Jucker
Title: Neurofilament light chain in blood serum as marker of disease progression in neurodegenerative diseases
Date of Request: June 29, 2016
Status:
ID: DIAN-T1606
Aim 1: Determine whether and how many years before the estimated time point of symptom onset (EYO) mutation carriers (MC) of autosomal dominant Alzheimer?s disease (ADAD) show altered blood (serum) levels of neurofilament light chain (NfL) compared to non-mutation carriers (nMC).
Aim 2: Test whether serum levels of NfL are correlated with previous measured CSF levels and are associated with longitudinal changes in PIB-PET, FDG-PET, and structural MRI, resting state fMRI, with other CSF biomarkers, clinical symptoms and performance
Aim 3:
Aim 4:
Investigator: Perminder S Sachdev
Title: Identification and preliminary validation of plasma protein, lipid and metabolite biomarkers in autosomal dominant Alzheimer?s disease
Date of Request: June 2, 2016
Status:
ID: DIAN-T1605
Aim 1: Identification of plasma protein biomarker candidates using two discovery proteomics approaches (iTRAQ and SWATH-MS)
Aim 2: Targeted proteomics for validation of protein biomarker candidates and comparison of proteins changes in ADAD and LOAD
Aim 3: Identification of metabolite biomarkers using targeted and non-targeted metabolomics
Aim 4: Investigate and validate lipid and metabolite alterations using liquid chromatography coupled with mass spectrometry (LC-MS) in autosomal dominant Alzheimers disease
Investigator: Assistant professor Henrietta M Nielsen, PhD
Title: CSF alpha-synuclein in familial versus sporadic AD
Date of Request: May 24, 2016
Status:
ID: DIAN-T1604
Aim 1: To assess CSF alpha-synuclein levels in patients with familial AD versus sporadic AD and controls
Aim 2: To investigate potential associations between CSF alpha-synuclein levels, AD biomarkers (piB-PET and CSF AD biomarkers) and cognitive status in familiar AD patients
Aim 3: To investigate potential effects of APOE genotype on CSF alpha-synuclein levels in familial versus sporadic AD patients
Aim 4:
Investigator: Suzanne Schindler
Title: Comparison of intra-individual change in INNOTEST CSF biomarkers in Autosomal Dominant Alzheimer Disease and Late Onset Alzheimer Disease
Date of Request: April 25, 2016
Status:
ID: DIAN-T1603
Aim 1: Aim 1: Characterization of intra-individual CSF biomarker changes
Aim 2: Aim 2: Correlation of CSF and imaging biomarkers of neurodegeneration
Aim 3: Aim 3: CSF biomarkers predict cognitive performance
Aim 4:
Investigator: Nikolaos Robakis
Title: Role of PS1 and FAD mutants on neuronal receptor complexes.
Date of Request: January 25, 2016
Status:
ID: DIAN-T1602
Aim 1: Examine role of PS1 and FAD mutants on neuronal receptor complexes and dimerization
Aim 2: Examine effects of PS1 and FAD mutants on the neuroprotective activities of BDNF and ephrins
Aim 3:
Aim 4:
Investigator: Mathias Jucker
Title: NfL in CSF of familial AD (DIAN)
Date of Request: January 7, 2016
Status:
ID: DIAN-T1601
Aim 1: to relate CSF NfL levels to the disease progression in familial AD
Aim 2:
Aim 3:
Aim 4:
Investigator: Christian Haass
Title: CSF Progranulin in autosomal dominant Alzheimer?s disease
Date of Request: December 24, 2015
Status:
ID: DIAN-T1506
Aim 1: Determine how cerebrospinal fluid (CSF) Progranulin levels change in relation to estimated years from expected symptom onset (EYO) in mutation carriers (MC) compared to non-carriers (NC)
Aim 2: Test whether CSF Progranulin levels are associated with cross-sectional and longitudinal changes in PIB-PET, FDG-PET, and structural MRI, rsfMRI, with other CSF biomarkers (Abeta42, T-tau, p-tau), clinical symptoms (MMSE, CDR-SOB) and cognitive performance (memory and executive functions).
Aim 3: Study the association of CSF Progranulin and CSF sTREM2
Aim 4:
Investigator: Eric A. Schon
Title: Diagnosis of AD based on perturbed MAM function in fibroblasts
Date of Request: December 3, 2015
Status:
ID: DIAN-T1505
Aim 1: To test the hypothesis that Alzheimer disease can be diagnosed in fibroblasts based on the analysis of phenotypes associated with increased ER-mitochondrial communication.
Aim 2:
Aim 3:
Aim 4:
Investigator: Dr Charlotte Warren-Gash
Title: HSV1 reactivation and clinical manifestation of autosomal dominant familiar Alzheimer?s disease
Date of Request: July 17, 2015
Status:
ID: DIAN-T1504
Aim 1: Overall aim: Investigate whether herpes simples virus 1 reactivation accelerates the onset or progression of dementia in individuals at risk from autosomal dominant Alzheimers disease.
Aim 2: Specific objectives:To measure serum IgG HSV-1 titres from serial samples collected from participants in the DIAN study
Aim 3: To compare rates of cognitive decline using standardised cognitive tests and quantitative brain atrophy measures in individuals with and without baseline HSV-1 IgG antibodies, using multiple linear regression models stratified by a range of potential confounders.
Aim 4: To assess whether the presence of IgG HSV-1 positivity results in earlier than predicted age of onset of clinical onset of AD in mutation carriers
Investigator: Felix Mueller-Sarnowski
Title: Progranuscreen – crossectional and longitudinal levels of progranulin and its relation to other markers of neurodegeneration
Date of Request: June 6, 2015
Status:
ID: DIAN-T1503
Aim 1: Crossectional and longitudinal description of progranulin levels of ADAD mutation carriers and mutation negative descendants of mutation carriers. Results are correlated with demographic, lab and imaging data.
Aim 2: To explore whether progranulin influences amyloid levels (blood and CSF) and amyloid deposition (shown by PIB-PET) as suggested by mouse models (Minami et al., Nature Medicine 2014).
Aim 3: Evaluation of progranulin as diagnostic and prognostic marker. Exploring the epidemiology of progranulin levels in different compartments of ADAD mutation carriers and healthy controls.
Aim 4: Identifying GRN mutation carriers as well as PGRN deficiencies that do not result from mutations for further investigations.
Investigator: Randall Bateman M.D.
Title: Dominantly Inherited Alzheimer’s Disease Protective Factor Study
Date of Request: February 17, 2015
Status:
ID: DIAN-T1502
Aim 1: To have tissue samples from at least 12 related family members analyzed by the Genome Institute at Washington University School of Medicine to look for any protective factor that may account for one family member not proceeding to signs of Alzheimer’s Disease 15 years over the age of onset 50
Aim 2: To create and administer questionnaires to at least 12 family members looking for an “incidence”, “factors such as environmental” etc that may explain the existance of a protective factor in one family member.
Aim 3:
Aim 4:
Investigator: Shauna Yuan
Title: In-vitro clinical trial with gamma-secretase modulators for the treatment of FAD carriers
Date of Request: February 2, 2015
Status:
ID: DIAN-T1501
Aim 1: Demonstration of target engagement for different FAD mutations
Aim 2: Evaluation of the effects of GSMs in human induced pluripotent stem cell in-vitro systems on downstream pathways affected in AD
Aim 3:
Aim 4:
Investigator: Jie Shen
Title: Effects of FAD PSEN1 mutations in mouse and human brains
Date of Request: December 11, 2014
Status:
ID: DIAN-T1407
Aim 1: To identify transcriptional alterations in sporadic and familial AD brains
Aim 2:
Aim 3:
Aim 4:
Investigator: Paul Thompson, Ph.D.
Title: Growth factors, neuroinflammation, exercise, and brain integrity
Date of Request: October 30, 2014
Status:
ID: DIAN-T1406
Aim 1: Determine how ADAD and APOE genetic status influence inflammation markers homocysteine, TNFα, BDNF, IGF-1, VEGF, Complement Factor H, SOD1, IL-13, and CCL1 relate to brain volume.
Aim 2: Determine how our ROI volumes relate to measures of exercise and how growth factors and TNFα modulate any relationship between exercise and these ROIs
Aim 3:
Aim 4:
Investigator: Carlos Cruchaga
Title: Identification of mutation-specific networks
Date of Request: October 29, 2014
Status:
ID: DIAN-T1405
Aim 1: To generate RNA-seq data from brain tissue from DIAN participants (mutation carriers and non-carriers)
Aim 2: To identify genes differentially expressed or spliced in mutation carriers vs LOAD, and vs controls
Aim 3: To identify gene and mutation-specific networks and pathways
Aim 4:
Investigator: Brian Gordon
Title: Insulin and glucose levels in autosomal dominant Alzheimer’s Disease
Date of Request: September 24, 2014
Status:
ID: DIAN-T1404
Aim 1: To measure fasting blood insulin and glucose levels in non-carriers, asymptomatic carriers, and symptomatic carriers
Aim 2: Relate alterations in insulin and glucose to biomarkers of AD pathology drawn from CSF, PET, and structural imaging
Aim 3:
Aim 4:
Investigator: Christian Haass
Title: Soluble TREM2 in autosomal dominant Alzheimer’s disease
Date of Request: April 17, 2014
Status: IP
ID: DIAN-T1403
Aim 1: Determine whether and how many years before the estimated time point of symptom onset (EYO), mutation carriers (MC) of autosomal dominant Alzheimerâs disease (ADAD) show altered cerebrospinal fluid (CSF) and plasma levels of soluble TREM2 (sTREM2) compared to non-mutation carriers (NC).
Aim 2: Test whether differences in CSF and plasma levels of sTREM2 are associated with longitudinal changes in PIB-PET, FDG-PET, and structural MRI, rsfMRI, with other CSF biomarkers (AÃ42, T-tau, p-tau), clinical symptoms (MMSE, CDR-SOB) and cognitive performance (memory and executive functions).
Aim 3:
Aim 4:
Investigator: Wyss-Coray
Title: plasma proteomic markers associated with CSF biomarkers in AD
Date of Request: March 17, 2014
Status: A
ID: DIAN-T1402
Aim 1: correlate CSF biomarkers with 700 plasma proteins using sliding threshold analysis
Aim 2: validate discovery of CSF Abeta threshold obtained with samples from sporadic AD
Aim 3: assess effects of APOE
Aim 4: find thresholds for tau, ptau and correlate plasma proteins with cognitive function
Investigator: Lucas Restrepo
Title: Antibody Signature of Alzheimer’s Disease
Date of Request: February 5, 2014
Status: IP
ID: DIAN-T1401
Aim 1: To confirm whether AD has a specific and reproducible antibody signature that can be used as diagnostic test
Aim 2: Confirm that patients with PSEN-1 mutations have an Alzheimer-type signature
Aim 3: Determine whether PSEN-2 and APP mutation carrieres have an Alzheimer signature
Aim 4: Determine whether Alzheimer signature is present before the onset of dementia in mutation carriers
Investigator: Randall Bateman
Title: DIAN TU Biomarker Core Validation Testing
Date of Request: June 5, 2013
Status: A
ID: DIAN-T1304
Aim 1: To develop and validate a method of measuring biomarker kit lot variability and new lot acceptance criteria
Aim 2: To establish and verify our internal quality control (QC) process for assay plate and sample acceptance criteria
Aim 3: To test DIAN TU drug interference on the ability of the AlzBio3 assay to detect CSF tau and ptau181
Aim 4: To validate the DIAN TU internal CSF pools as suitable internal controls to be used for Incurred Sample Reanalysis (ISR) during the trial
Investigator: Ajay Verma MD Ph.D., VP, Development Sciences Biogen Idec
Title: Proposal to evaluate the prognostic and diagnostic potential of selected AD biomarkers using plasma and CSF samples from DIAN registry
Date of Request: April 11, 2013
Status: IP
ID: DIAN-T1303
Aim 1: Evaluate total pyroglutamate-Aβ(pE3-Aβ) in plasma and CSF and other selected amyloid Aβ isoforms in CSF as prognostic/diagnostic markers of AD in symptomatic and pre-symptomatic populations of mutation carriers and non-carriers in the DIAN registry
Aim 2: Evaluate the CSF sTREM2 and VLP-1 markers as prognostic/diagnostic markers of AD in symptomatic and pre-symptomatic populations of mutation carriers and non-carriers in the DIAN registry
Aim 3: Evaluate the selected modified by oxidative stress tyrosine moieties in CSF as markers linked to amyloidogenesis, inflammation, and neuronal injury
Aim 4: Publish the findings from the above evaluations and share the results with Alzheimer’s disease research community
Investigator: Karen H. Ashe
Title: Specific CSF Abeta oligomers in unimpaired DIAN subjects
Date of Request: March 26, 2013
Status: A
ID: DIAN-T1302
Aim 1: Compare CSF Abeta*56 and Abeta trimer levels in unimpaired carriers and non-carriers
Aim 2: Correlate CSF Abeta oligomers with Abeta1-42, tau and p-tau181
Aim 3: Relate CSF Abeta*56 and Abeta trimer levels to predicted age of onset
Aim 4:
Investigator: Richard J. Perrin
Title: Quantitative label-free proteomics for CSF Biomarkers in Dominantly Inherited AD
Date of Request: February 6, 2013
Status: A
ID: DIAN-T1301
Aim 1: To evaluate and map the temporal patterns of novel CSF biomarkers, measured in DIAN samples using quantitative label-free proteomics. Data will be aligned according to expected symptom onset; values from carriers (N=120) and non-carriers (N=80) will be compared (as in Bateman RJ, et al. NEJM 2012).
Aim 2: To integrate proteomics data into the context of known AD-associated changes for this cohort (Bateman RJ, NEJM 2012), to compare novel and existing markers, and to compare this autosomal dominant dataset to a sporadic AD dataset already derived from proteomic analysis of a Knight ADRC cohort.
Aim 3:
Aim 4:
Investigator: John M. Ringman, M.D., M.S.
Title: Metabolic profiling of biofluids in Alzheimer’s Disease
Date of Request: November 15, 2012
Status: A
ID: DIAN-T1206
Aim 1: Identify the compounds in the combined gas chromatography-mass spectrometry profiles that differentiate the samples collected from patients carrying and not carrying causative FAD mutations. Further analyses will compare presymptomatic and symptomatic persons carrying FAD mutations.
Aim 2: Identify peaks in the combined liquid chromatography-mass spectrometry profiles that differentiate samples collected from causative FAD mutation carriers and non-carriers, and presymptomatic and symptomatic FAD mutation carriers and identify the responsible compounds.
Aim 3: Establish and apply quantitative assays to the compounds identified in Aims 1 and 2.
Aim 4: Integrate all the compounds that are identified in Aims 1 and 2 into a biochemical overview, and rationalize these data with the extant knowledge about Alzheimer’s Disease pathology.
Investigator: Alison Goate
Title: Defining the mechanisms of AD pathogenesis in human IPSC-derived neurons
Date of Request: November 5, 2012
Status: A
ID: DIAN-T1204
Aim 1: To measure the influence of pathogenic FAD mutations on APP and tau metabolism in human neurons
Aim 2:
Aim 3:
Aim 4:
Investigator: Marc I. Diamond
Title: Seeding of Tau Aggregation: A Novel Plasma and CSF Biomarker for Alzheimer’s Disease
Date of Request: October 13, 2012
Status: A
ID: DIAN-T1203
Aim 1: 1) To determine the sensitivity and specificity of our seeding assay for identifying subjects with AD.
Aim 2: 2) To determine when in the course of the disease process the seeding assay becomes positive.
Aim 3: 3) To examine how seeding activity correlates with validated biomarkers in a well-studied population.
Aim 4:
Investigator: Odity Mukherjee
Title: Development and characterization of iPS derived cellular model for Alzheimer’s Disease
Date of Request: March 10, 2012
Status: IA
ID: DIAN-T1202
Aim 1: We are a group working on the molecular and functional characterization of neuropsychiatric illness using patient specific cellular models. LCl lines from the DIAN repository are fully characterized and would serve as informative control in our attempts to model disease phenotypes.
Aim 2:
Aim 3:
Aim 4:
Investigator: Prof. Ralph Martins
Title: Investigating blood and CSF lipid biomarkers in autosomal dominantly inherited Alzheimer’s disease.
Date of Request: January 28, 2012
Status: IA
ID: DIAN-T1201
Aim 1: Identify early modifications in plasma, CSF and platelet lipid profiles of DIAN participants which may reveal critical information about the pathobiological cascade that culminates in symptomatic disease.
Aim 2: Demonstrate any correlation that may exist across the two major macromolecule subclasses in the blood and CSF, i.e. lipids and selected proteins (Aβ, ApoE, phospho and total tau) and also contribute to a panel of biomarkers to detect AD through a blood test.
Aim 3: Correlate the DIAN lipid profile with brain imaging data obtained from MRI, FDG-PET and PiB-PET scans and determine whether there exists a link between biochemical alterations occurring in the periphery and brain.
Aim 4:
Investigator: Bernadino Ghetti
Title: Neuropathological findings of brains of persons with familial AD (FAD) due to the A431E PSEN1 mutation
Date of Request: December 5, 2011
Status: A
ID: DIAN-T1102
Aim 1: To thoroughly characterize and describe the neuropathological findings of 11 brains of persons with familial AD (FAD) due to the A431E PSEN1 mutation.
Aim 2: To correlate pathological findings with clinical findings in these patients.
Aim 3: To explain specific clinical and imaging features of the A431E mutation by quantifying aspects of the neuropathology.
Aim 4:
Investigator: Dave Holtzman
Title: Assessment of CSF YKL-40, VILIP-1, and calbindin as diagnostic and prognostic markers
Date of Request: December 5, 2011
Status: A
ID: DIAN-T1101
Aim 1: Examine the utility of CSF VILIP-1, YKL-40, and calbindin D28K (alone or in combination with CSF tau, p-tau181, and A?42) in the identification of mutation carrier status in family members of individuals with familial AD compared to non-mutation carrier status.
Aim 2: Investigate whether CSF levels of VILIP-1, YKL-40, and calbindin D28K (alone or in combination with CSF tau, p-tau181, and A?42) can predict symptomatic onset over the study follow-up period.
Aim 3: Determine whether CSF levels of VILIP-1, YKL-40, and calbindin D28K correlate with other CSF and imaging markers of preclinical AD pathology such CSF tau, p-tau181, A?42, and amyloid load on PET-PIB in familial AD.
Aim 4: