Center for Alzheimer's and Related Dementias: First stage single-cell brain resource for Alzheimer's disease and related dementias

National Institute On Aging

Investigators

Abstract

We have generated single nuclei ATACseq (snATAC) and RNAseq (snRNA) data from over 350 brain samples from the prefrontal cortex of neurologically healthy individuals. We worked in collaboration with the CARD Advanced Analytics team to identify cell type relevant Quantitative Trait Loci (QTL) and genes and genomic regions that are associated with aging in different cell types. We have replicated known associations and identified numerous new lines of research. This work involved a protocol optimization period and extensive optimization of analysis workflows, which can also be applied to additional brain regions. A manuscript is in preparation for the prefrontal cortex samples. We have also collected multiome data from 140 substantia nigra samples from diseased (Parkinson's disease, Dementia with Lewy Bodies), and 75 age-matched neurologically healthy controls, as well as from hippocampal tissue in 100 cases (Alzheimer's disease and Dementia with Lewy Bodies) and 100 age-matched neurologically healthy controls. The multiome data generated from the three regions will be made available to the scientific community. All pipelines developed for this project will be available on Github as community tools. These results will be used to better understand the transcriptional regulatory networks and cis regulatory networks that are involved in the cell types affected by disease. The project represents a significant investment in understanding the cellular mechanisms underlying Alzheimer's disease and related dementias through comprehensive single-cell analysis of affected brain tissue. Manuscripts in progress: Catching, A., et. al. "Single nucleus multiome analysis in the human pre-frontal cortex identifies features associated with aging in multiple genetic populations" Jiang, R., et. al. "Single nucleus multiome analysis in the human hippocampus of AD/ADRD connects novel pathyways to disease pathogenesis"