Basic Science and Pathogenesis.

Background: Single-nucleus RNA sequencing (snRNAseq) allows for the dissection of the cell type-specific transcriptional profiles of tissue specimens. In this study, we compared gene expression in multiple brain cell types in brain tissue from Alzheimer disease (AD) cases with no or other co-existing pathologies including Lewy body disease (LBD) and vascular disease (VaD).

Method: We evaluated differential gene expression measured from single nucleus RNA sequencing (snRNAseq) data generated from the hippocampus region tissue donated by 11 BU ADRC participants with neuropathologically confirmed AD with or without a co-existing pathology (AD-only = 3, AD+VaD = 6, AD+LBD = 2).

Basic Science and Pathogenesis.

Background: Some subjects exhibit AD pathology but remain cognitively intact. This resilience has been associated with cell-type abundance changes, particularly in neurons. We investigated the molecular basis of cognitive resilience by deconvoluting bulk RNA sequencing (RNA-seq) data into multiple brain cell types derived from three brain regions.

Cognitive resilience to Alzheimer's disease characterized by cell-type abundance.

Introduction: The molecular basis of cognitive resilience (CR) among pathologically confirmed Alzheimer's disease (AD) cases is not well understood.

Methods: Abundance of 13 cell types and neuronal subtypes in brain bulk RNA-seq data from the anterior caudate, dorsolateral prefrontal cortex (DLPFC), and posterior cingulate cortex (PCC) obtained from 434 AD cases, 318 cognitively resilient AD cases, and 188 controls in the Religious Orders Study and Rush Memory and Aging Project was estimated by deconvolution.

Results: PVALB+ neuron abundance was negatively associated with cognitive status and tau pathology in the DLPFC and PCC (P< 0.

Molecular Quantitative Trait Locus Mapping in Human Complex Diseases.

Mapping quantitative trait loci (QTLs) for molecular traits from chromatin to metabolites (i.e., xQTLs) provides insight into the locations and effect modes of genetic variants that influence these molecular phenotypes and the propagation of functional consequences of each variant.