Genetic variants associated with Alzheimer's disease confer different cerebral cortex cell-type population structure.

ABSTRACT:

Background

Alzheimer's disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, the specific effects that pathological mutations and coding variants associated with AD have on the cellular composition of the brain are often ignored.

Methods

We developed and optimized a cell-type-specific expression reference panel and employed digital deconvolution methods to determine brain cellular distribution in three independent transcriptomic studies.

Results

We found that neuronal and astrocyte relative proportions differ between healthy and diseased brains and also among AD cases that carry specific genetic risk variants. Brain carriers of pathogenic mutations in APP, PSEN1, or PSEN2 presented lower neuron and higher astrocyte relative p

SUBMITTER: Li Z 

PROVIDER: S-EPMC5992755 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature