ABCA7 Loss-of-Function Variants Impact Phosphatidylcholine Metabolism in the Human Brain.

ABSTRACT: Loss-of-function (LoF) variants in the lipid transporter ABCA7 significantly increase Alzheimer's disease risk (odds ratio ≈ 2), yet the underlying pathogenic mechanisms and specific neural cell types affected remain unclear. To investigate this, we generated a single-nucleus RNA sequencing atlas of 36 human postmortem prefrontal cortex samples, including 12 carriers of ABCA7 LoF variants and 24 matched non-carriers. ABCA7 LoF variants were associated with transcriptional changes across all major neural cell types. Excitatory neurons, which expressed the highest levels of ABCA7, showed significant alterations in oxidative phosphorylation, lipid metabolism, DNA damage responses, and synaptic signaling pathways. ABCA7 LoF-associated transcriptional changes in neurons were similarly pe

SUBMITTER: von Maydell D 

PROVIDER: S-EPMC11230156 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature