The Knight ADRC has supported many investigators at Washington University and at other institutions over the years. We wish to avoid the situation where two investigators study the same research question to avoid duplication of effort and potential conflict. To determine if your topic has already been studied with our resources, please search our database. If you find that your topic or a related topic has been submitted, you may wish to contact the investigator to inquire about their 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 number (e.g. T1004), the full request has been submitted and is either approved, disapproved or in process. If an entry has no ID number, then it represents a submission that has not yet been reviewed. Search terms are applied across an entire requests application including variables not displayed below. A more specific, detailed search may yield better results depending upon your needs.
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Investigator: Diana Farmer/Aijun Wang (mPI)
Project Title: Engineered Targeted Extracellular Vesicles for Neurovascular Unit Restoration in Brain Organoid Model of Alzheimer’s Disease
Date: June 19, 2022
Request ID: T2215
Aim 1: Generate Ex Vivo Model of Alzheimer’s disease Using Human Brain Organoids Derived from Induced Pluripotent Stem Cells
Aim 2: Examine preferential neuron uptake, reduced blood-brain barrier permeability, increased angiogenesis, and glial cell modulation by astrocyte-derived extracellular vesicles in human brain organoid model
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Investigator: Alison M. Goate
Project Title: Uncovering the genetic mechanisms of the Chromosome 17q21.31 Tau haplotype on neurodegeneration risk in FTD and PSP
Date: June 16, 2022
Request ID: T2213
Aim 1: Define changes in gene regulatory architecture and expression in FTD-tau.
Aim 2: Characterize the parallel gene regulatory and expression relationships, and FTDassociated Tau phenotypes in 3D assembloids harboring FTD-causing MAPT mutations on both the H1/H1 and H2/H2 backgrounds.
Aim 3: Characterize the functional consequences of key haplotype-associated regulatory (enhancer/repressor) regions containing candidate causal common variants, as well as their effects on rare mutations.
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Investigator: Yanzhuang Wang
Project Title: Golgi Defects as a novel biomarker for the Diagnosis of Alzheimer’s Disease
Date: June 12, 2022
Request ID: T2214
Aim 1: Establish cell lines with fluorescently labeled Golgi
Aim 2: Optimize the assay
Aim 3: Test the effect of human AD samples on the Golgi morphology
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Investigator: Owen Ross, PhD
Project Title: Determining the molecular etiology of Pick’s disease
Date: May 13, 2022
Request ID: T2212
Aim 1: To identify and collect samples of brain tissue from pathologically confirmed PiD cases.
Aim 2: Using DNA extracted from these samples, to perform genome-wide genetic assessments associated with Pick’s disease risk, progression, and pathological severity to better understand disease etiology.
Aim 3: To use multi-omic approaches to characterize the transcriptome, proteome, lipidome and metabolome of brain tissue from PiD cases.
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Investigator: Ann McKee, MD
Project Title: The Contribution of Age-Related Tauopathies to Alzheimer’s Disease: ART-AD
Date: April 27, 2022
Request ID: T2211
Aim 1: To determine the frequency of age-related tauopathy among individuals with normal cognition, mild cognitive impairment (MCI) and dementia.
Aim 2: To apply information from this project to develop standardized assessment modules for age-related primary tauopathy.
Aim 3: Our long-term goal is for these protocols to be deployed for general use across NIH-funded brain banks.
Aim 4: To digitize and score tissue sections by a panel of neuropathologists expert in neurodegeneration/tauopathy to determine the frequency of age-related tauopathies in each clinical subgroup.
Investigator: Suzanne Schindler
Project Title: Prediction of cognitive decline with plasma p-tau181, p-tau217 and brain MRI
Date: April 21, 2022
Request ID: T2210
Aim 1: We hypothesize that plasma p-tau181 and p-tau217 will distinguish amyloid PET status with a ROC AUC of >0.85.
Aim 2: We hypothesize that plasma p-tau181 and p-tau217, amyloid PET and/or brain MRI* will distinguish cognitively normal from cognitively impaired individuals with a ROC AUC >0.80.
Aim 3: We hypothesize that plasma p-tau181 and p-tau217, amyloid PET and/or brain MRI* will identify cognitively normal individuals who progress to symptomatic AD (MCI or dementia) with a ROC AUC of >0.85.
Aim 4: We hypothesize that plasma p-tau181 and p-tau217, amyloid PET and/or brain MRI* will be significantly associated with cognitive decline (MMSE and PACC) in cognitively normal, amyloid PET positive individuals.
Investigator: Nilufer Ertekin-Taner
Project Title: Centrally-linked Longitudinal pEripheral biomARkers of AD (CLEAR-AD) in multi-ethnic populations
Date: April 12, 2022
Request ID: T2209
Aim 1: Discover brain region and cell-specific molecular signatures of disease, and related endophenotypes, using single nucleus RNAseq (snRNAseq) and bulk tissue profiling of transcriptome, methylome, proteome, lipidome/metabolome data from 5 brain regions.
Aim 2: Identify molecular signatures preserved between brain and blood, using transcriptome, methylome, proteome, lipidome/metabolome data from antemortem blood collected on the same participants studied in Aim 1.
Aim 3: Discover molecular signatures that reflect biological subtypes and temporal progression of AD by performing integrative multi-omics analysis with endophenotypes including local neuropathology and antemortem longitudinal assessments.
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Investigator: Kristine Wylie and Russell Nicholls
Project Title: Exploring the contribution of viral PP2A inhibition to tau pathology in Alzheimer’s disease
Date: April 8, 2022
Request ID: T2208
Aim 1: Compare the prevalence of PP2A inhibiting viruses in tissue in samples obtained from human brains at sites with and without tau pathology
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Investigator: Nilufer Ertekin-Taner
Project Title: Centrally-linked Longitudinal pEripheral biomARkers of AD (CLEAR-AD) in multi-ethnic populations
Date: March 1, 2022
Request ID: T2207
Aim 1: To evaluate the association of blood gene co-expression networks with AD and AD endophenotypes, utilizing RNAseq data generated from African American and Latino American ADRC participants who have donated PAXgene blood RNA tubes.
Aim 2: To evaluate the association of methylation changes with AD and AD endophenotypes, utilizing blood methylome data generated from African American and Latino American ADRC participants included in Aim 1.
Aim 3: To identify blood multi-omics molecular signatures that are strongly associated with AD diagnosis/endophenotypes, by integrating RNAseq and methylome results from Aims 1 and 2, with other available -omics datasets.
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Investigator: Guojun Bu
Project Title: Biology and pathobiology of apoE in aging and Alzheimer’s disease (APOE U19 Core C: Neuropathology Core)
Date: February 16, 2022
Request ID: T2206
Aim 1: Provide postmortem human brain tissue for biochemical and biophysical studies of apoE-lipoprotein particles (Core B) and for multi-omics studies (Core F) to define APOE-, aging-, and sex-dependent effects.
Aim 2: Perform ELISA assays to quantify levels of apoE, Aβ, tau, synaptic markers, glial activation markers, inflammatory cytokines, vascular markers, and other aging- and AD-related molecules in selected brain regions in AD and control brains.
Aim 3: Examine the association of APOE genotype with comorbid pathologies, including Aβ deposits and CAA, non-Alzheimer neuronal and glial tau pathologies, α-synuclein pathology and TDP-43 proteinopathy in AD and control brains.
Aim 4: Investigate neuropathologic phenotypes associated with novel genetic loci that modify APOE risk for AD identified in Project 5.