Search DIAN Tissue Requests
Johannes Levin
Molecular detection of α-synuclein co-pathology in ADAD mutation carriers
04/29/2021
approved
DIAN-T2104
Use real time quaking induced conversion (RT-QuIC) for ante mortem detection of Synuclein pathology in ADAD mutation carriers
Compare the data from RT-QuIC regarding in vivo detection of Synuclein pathology with data from post mortem examinations (manuscript in preparation).
Within the time frame of 15 years EYO we will analyse the time-point of emergence of LB pathology as measured by RT-QuIC .
We will analyse clinical and imaging data longitudinally comparing RT-QuIC positive and RT-QuIC negative participants.
Mariah S. Hahn
Targeting Dysregulated Synapse and Proteostasis Mechanisms in Alzheimer's Disease
06/03/2021
approved
DIAN-T2105
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.
Randall J Bateman
Comprehensive analyses of the soluble microtubule binding region (MTBR)in Alzheimer disease progression.
09/02/2021
approved
DIAN-T2106
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).
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.
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.
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:
Ronald Davis
Capturing the mitochondrial complexity in familial Alzheimer's disease
09/15/2021
pending
DIAN-T2107
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.
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
Dan Nicholson
High-resolution multiplex localization of Alzheimer’s disease risk and resilience factors
09/23/2021
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).
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).
Cruchaga
Multi-Omics CSF and plasma signature of ADAD
10/16/2021
To identify ADAD-specific multi-omic (proteomics and metabolomic) signatures CSF and plasma
To identify multi-omic (metabolomics and proteomics) plasma signatures and QTLs in ADAD
Jee Hoon Roh/Jae-Hong Lee
Epigenetic analyses to assess the resilience among DIAN mutation carriers
12/15/2021
To investigate the potential epigenetic causes of resilience among DIAN mutation carriers who are discordant in disease courses measured by biomarkers.
Giuseppina Tesco
Study of endolysosomal alterations (including exosomes) in brain cells cultures derived from fDA iPSC lines and isogenic controls
01/25/2022
approved
DIAN-T2201
Determine the effect of mutant APP on exosome dynamics in CNS cells in human AD models.
Antonio Boza Serrano
Galectin-3 as a prognostic biomarker to monitor Autosomal dominant Alzheimer's Disease's progression
04/27/2022
not approved
DIAN-T2202
We aim to evaluate if gal3 levels are elevated in ADAD and if they might track the progression of AD pathology.
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
Patrick Oeckl
Investigation of plasma Beta-Synuclein levels in asymptomatic and symptomatic autosomal dominant Alzheimer´s disease
06/20/2022
approved
DIAN-T2204
To investigate if blood levels of the synaptic marker Beta-Synuclein are already elevated in asymptomatic ADAD
To estimate a time course of blood Beta-Synuclein changes in ADAD based on EYO and comparison with other blood/CSF biomarkers
Relationship of blood Beta-Synuclein levels in ADAD with other fluid and imaging biomarkers, brain atrophy and cognitive impairment