Search DIAN-TU Biospecimen Resource Requests
NA
Imaging-Histology Comparisons of Tau Pathology in ADAD and LOAD
04/21/2020
Approved
DR_001
Perform a quantitative comparison of tau pathology in ADAD and LOAD using imaging and histology
NA
Proposal for comparison between Dominantly Inherited Alzheimer Disease and sporadic early-onset Alzheimer’s disease
05/20/2020
Pending
DR_002
To compare clinical presentation, neuropsychological performance and cognitive decline rate between DIAD and sporadic EOAD
To examine in vivo the regional distribution of tau, amyloid-beta, brain glucose metabolism, and structural atrophy, as well as their relationships, in DIAD and sporadic EOAD
To compare CSF biomarkers levels and rates of change in DIAN and sporadic EOAD
Suman Jayadev
Peripheral immune profiles in ADAD
04/20/2021
Pending
DR_016
Measure immune related microRNA, exosome, proteins in carriers and non-carriers
Yan Li
Gain Precision on the Measurement of Cognitive Impairment – Item Response Theory Scoring of the CDR
05/11/2021
Pending
DR_011
Evaluate the difficulty and discrimination level, and the longitudinal change of each item in CDR and their longitudinal change over time
Develop the best fitting item response theory (IRT) model for automatically scoring dementia severity (IRT score)
Compare the performance of the IRT score with that of the CDR sum of box in terms of powering a clinical trial and precision in tracking cognitive change over time, especially for cognitively normal participants
Valid the performance of the IRT score using other psychometric measures and biomarkers.
Mariah S. Hahn
Targeting Dysregulated Synapse and Proteostasis Mechanisms in Alzheimer's Disease
06/01/2021
Referred to Obs
DR_012
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.
Compare AD_(PSEN1)-iNeuron cultures to iNeuron cultures derived from unaffected family member controls with respect to Aβ, tau phosphorylation, synapse maintenance and proteostasis.
N/A
Relationship between regional baseline and longitudinal tau PET SUVR, and correlations with change in cognition in participants from the DIAN-TU study
07/19/2021
Approved
DR_013
Characterize the spatial patterns of tau deposition at baseline and over time in the DIAD population
Estimate the rate of change in tau deposition in DIAD participants in each of the provided parcellated brain regions
Identify the (meta)ROI(s) at baseline that best correlate with change in tau PET SUVR and change in cognition, respectively, over time
Characterize the relationship between change in tau PET SUVR and change in cognition (and other biomarkers)
Ron Davis
Unraveling the complexity of mitochondrial pathology in familial Alzheimer's disease
09/14/2021
Referred to Obs
DR_014
Use high-content and high-throughput assay to quantify the MT dynamics phenotypes that develop in neurons derived from iPSCs of fAD subjects and age-matched and/or isogenic controls.
Define the functional impairment in these neurons (IMM-inner mitochondrial membrane potential).
Interrogate the function of the electron transport chain (ETC) in these neurons.
Measure the structural integrity of MT, the ETC, and MT-related processes in these neurons by quantitative Western blotting of proteins and/or tandem mass tag quantitative mass spectroscopy.
Antonio Boza-Serrano
Galectin-3 as a prognostic biomarker to monitor Autosomal dominant Alzheimer Disease’s progression and response to gantenerumab.
10/29/2021
Pending
DR_015
To evaluate if gal3 levels in ADAD samples might track /monitor the progression of AD pathology and whether or not gal3 levels are altered under the different treatment evaluated with the patients (gantenerumab)
To compare the levels of gal3 with the classic biomarkers of pathology progression (amyloid-beta 42, total tau, p-tau181, NfL and PIB-Pet) evaluated in CSF and serum over the DIAN-TU study in placebo, ganterenumab treated patients.
Jan Torleif Pedersen, PhD MSc
Investigation of pS396-tau in samples from DIAN-TU biobank
12/03/2021
Referred to Obs
DR_017
To investigate pS396-tau levels in CSF samples from DIAN-TU
To investigate pT217-tau levels in CSF samples from DIAN-TU
To establish potential correlation between pS396-tau, pT217-Tau and clinical progression parameters
To investigate tau species in post-mortem brain material targeted by Lu AF87908
Colin Masters
CSF Abeta42 and p-tau level review
12/08/2021
DR_018
To provide further information regarding ex-participant 3031007's mutation and pathogenic status. V2 28 May15 CSF Abeta42 and p-tau levels to be reviewed.
Giuseppina Tesco
Study of endolysosomal alterations (including exosomes) in brain cells cultures derived from fDA iPSC lines and isogenic controls
01/24/2022
Referred to Obs
Study of endolysosomal alterations (including exosomes) in brain cells cultures derived from fDA iPSC lines and isogenic controls
Bateman/Benzinger
ASNR White Paper on ARIA
02/08/2022
Training of Radiologists and Neuroradiologists
Enhance physician understanding of ARIA in order to improve detection and reporting. Additionally, the objective is to provide physicians with imaging examples of the severity grading of ARIA as well as pointing out potential pitfalls in interpretation
Ifrah zawar
Csf biomarkers in seizures among AD patients
04/11/2022
Closed
DR_020
To study the differences in csf biomarkers in AD patients with and without seizures
Jinlong Yu
Install APP A673T mutation for treatment of AD
05/20/2022
DR_022
To optimize the base editor condition in AD patients IPSC derived neurons.
Test if the additional E674K mutation base editing introduced modulates the Aβ peptides production and Aβ peptides ‘s toxicity
David Gate
Comparing active and passive Abeta vaccination by spatial transcriptomics
07/25/2022
Identify spatial transcriptomic changes associated with Aβ vaccination.
Tammie Benzinger
Quantification of Neuroinflammation in Autosomal Dominant Alzheimer's Disease Using Small-block Brain Specimen imaged by Diffusion Basis Spectrum Imaging (DBSI)
08/16/2022
assess the value of DBSI for the study of ADAD by comparing post-mortem MRI signals with histologic data
RANDALL J BATEMAN
DIAN-TU-001 Clinical Core Statistical Analysis Plan (SAP) for biochemical measures of amyloid and tau phosphorylation in the brain, and their correlation with clinical, cognitive, and other imaging/CSF outcomes
01/17/2023
Specific Aim 1: To biochemically quantify the amount of soluble and insoluble amyloid-beta and tau species in specific regions of the frozen brain regions by mass spectrometry in DIAN-TU, DIAN-Obs and non-AD age-matched controls. Additional biochemical measures of other biomolecules, for example, alpha synuclein, APP, ApoE, inflammatory markers, synaptic & neuronal markers will also be explored.
Specific Aim 2: Compare the amounts of soluble and insoluble amyloid-beta and tau species between active gantenerumab, active solanezumab, placebo (those from the DIAN-TU placebo arm who did not continue in the gantenerumab Open Label Extension, when available), and control cases (including DIAN-Obs and non-AD controls) to determine effects of drug treatment on amyloid-beta and tau species. Active drug data will be compared with placebo and controls, not with other drug data.
Specific Aim 3: To quantify by immunohistochemistry the amount of amyloid-beta deposition, tau pathology, astrocytosis, microgliosis, alpha-synucleinopathy, and TDP-43 proteinopathy in multiple neuroanatomic regions of the formalin-fixed brain tissue samples from DIAN-TU and DIAN-Obs participants and their family members, and non-AD age-matched controls. Additional immunohistochemistry measures of other biomolecules, for example, APP, ApoE, inflammatory markers, synaptic & neuronal markers will also be explored.
Specific Aim 4: Evaluate how amyloid-beta and tau species in insoluble and soluble fractions of the brain and pathologic features measured by immunohistochemistry in formalin-fixed brain tissue are correlated with each other, as well as with the cross-sectional value and longitudinal changes in other imaging/CSF biomarkers (e.g., amyloid PET, tau PET, CSF amyloid-beta, total tau, and phospho-tau), and with clinical and cognitive outcomes, and how these correlations are altered by the active treatments.
Carlos Cruchaga
Functional characterization of brain circular RNAs in Alzheimer disease using induced pluripotent stem cell models
04/04/2023
To analyze the role of circHOMER1 in AD-related molecular phenotypes using cellular models
Bart De Strooper
Testing the role of presenilins in cell states
04/14/2023
Profiling the gamma-secretase substrate proteome in PSEN1 H163R iPSC-derived microglia
Characterizing the transcriptional and functional phenotype of human PSEN1 H163R microglia in a humanized chimeric AD mouse model.
Junie Saint Clair
Examining the Predictive Value of Synaptic Dysfunction and Neuronal Injury Measures on Imaging Markers of Disease Presentation and Progression in Alzheimer's Disease
08/01/2023
Evaluate association between rates of longitudinal change in CSF levels of Ng, SNAP-25, VILIP-1 and imaging brain changes and cognition in a DIAD cohort.
Evaluate association between rates of longitudinal change in CSF levels of Ng, SNAP-25, VILIP-1 and imaging brain changes and cognition in aged adults LOAD cohort.
Randall Bateman
Proteomic Biomarkers in Autosomal Dominant Alzheimer’s Disease
08/07/2023
Define the landscape and temporal sequence of CSF and plasma proteomic changes in ADAD
Determine how treatment with anti-amyloid immunotherapies affects levels of brain-based biomarkers in ADAD CSF and plasma
Leverage proteomics data to provide biological pathway and systems context to experimental results generated in other DIAN projects
Laurent Roybon
Models and therapies for Dominantly Inherited Alzheimer disease
08/16/2023
Generate humanized models of early and advanced AD cellular pathogenesis
Use humanized models to explore a gene therapy for disease progression in AD
NA
Review of ARIA in Japanese
10/02/2023
We want to use DIAN's images from an article in our review article
We want to use the images to illustrate actual symptoms
Colin Masters
Automated detection and reporting of amyloid-related imaging abnormalities (ARIA) with emerging Alzheimer's disease therapeutics
10/12/2023
To develop automated machine learning algorithms for detection and reporting of ARIA using serial MRI scans of patients who underwent treatment with an anti-Aβ antibody therapy.
To identify the potential AD biomarkers that are associated with an increased risk of ARIA development.
Determine the level of autoantibodies to Abeta in the baseline and follow up plasma who are being treated with an anti-Abeta antibody therapy.
Jorge J Llibre Guerra & Clara Vila-Castelar
Influence of biological sex in response to treatment in Autosomal Dominant Alzheimer’s Disease
10/27/2023
To describe sex differences in cognitive outcomes between women and men
To investigate possible differences in PiB-PET, brain glucose metabolism, and structural atrophy rate of change between women and men.
To compare fluid biomarker levels and rates of change between women and men in DIAN-TU double blind period of gantenerumab or solanezumab.