Overview
Description
The search for novel risk factors for Alzheimer disease relies on access to accurate and deeply phenotyped datasets. The Memory and Aging Project at the Knight-ADRC (Knight ADRC-MAP) collects plasma, CSF, fibroblast, neuroimaging clinical and cognition data longitudinally and autopsied brain samples. We are using multi-tissue (brain, CSF and plasma) multi-omic data (genetics, epigenomics, transcriptomics, proteomics and metabolomics) to identify novel risk and protective variants, create new prediction models and identify drug targets. The study cohort includes MAP participants from the Knight-ADRC at Washington University in St. Louis (MO). MAP participants have to be at least 65 years old and have no memory problems or mild dementia at the time of enrollment. There is no age at onset criteria for this cohort. Cases had to have a CDR >=0.5 whereas controls had to have a CDR=0 at last assessment. AD definition is based on a combination of both clinical and pathological information if available. Pathologic diagnosis will overrule clinical diagnosis. Participants are Non-Hispanic white from North America (95%) and African American (5%). Autopsy information was provided if available, but it is not a requirement for enrollment.
Additional information about Knight ADRC datasets available through NIAGADS can be found on the Knight ADRC Collection page.
Principal Investigators
Carlos Cruchaga, Ph.D.
Washington University in St. Louis
Maria Victoria Fernandez, Ph.D.
Washington University in St. Louis
Oscar Harari, Ph.D.
Washington University in St. Louis
Funding Sources
National Institutes of Health (R01-AG044546, P01-AG003991, RF1-AG053303, NIH P50-AG05681, P01-AG026276, U24-AG21886, U24-AG026395 and U01-AG058922).
The Alzheimer Association (NIRG-11-200110, BAND-14-338165 and BFG-15-362540).
Publications
- Fernández MV. SORL1 variants across Alzheimer's disease European American cohorts. European journal of human genetics : EJHG. 2016 Dec. PubMed link
- Cruchaga C. Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2018 Feb. PubMed link
- Fernández MV. Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. PLoS genetics. 2017 Nov. PubMed link
- Ridge PG. Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer's disease resilience. Genome medicine. 2017 Nov 29. PubMed link
- Fernández MV. Evaluation of Gene-Based Family-Based Methods to Detect Novel Genes Associated With Familial Late Onset Alzheimer Disease. Frontiers in neuroscience. 2018. PubMed link
- Yang C. Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders. Nature neuroscience. 2021 Sep. PubMed link