Allele specific expression in Alzheimer's disease

Allele-specific expression (ASE), preferential expression of one allele at a heterozygous locus, is implicated in various brain diseases but remains largely uncharacterized in Alzheimer's disease (AD).

We performed a genome-wide characterization of ASE variants across seven brain regions of 2,231 AD and Control patients from Mount Sinai Brain Bank (MSBB) and Religious Orders Study/Memory and Aging Project (ROSMAP) cohorts and investigated cell-type-specific activity via single-cell analysis.

We identified 56,136 unique ASE variants that were enriched in imprinted chromosomal regions, e.g., chr6, chr14q32, and chr15q11. ASE variants were also found in exons of known AD-associated genes, including apolipoprotein E (APOE), CLU, CTSB, and HLA-DRB1. Forty variants exhibited AD-associated ASE, and the affected genes, including SLC12A5, SYT13, and TOMM7, were predominantly downregulated in multiple cell types, including astrocytes, excitatory neurons, and oligodendrocytes.

We provided a detailed landscape of ASE in AD, uncovering novel functional variants and highlighting their potential cell-type-specific contributions to disease pathogenesis.