Neuronal ABCA7 deficiency aggravates mitochondrial dysfunction and neurodegeneration in Alzheimer's disease.

ABSTRACT:

Introduction

Loss-of-function variants of the ABCA7 gene are associated with an increased risk of Alzheimer's disease (AD). How neuronal ABCA7 contributes to AD pathogenesis is unknown.

Methods

Using neuron-specific Abca7 KO mice (nAbca7^-/-) with or without 5×FAD amyloid model background and post mortem AD brains, we investigated AD-related phenotypes through comprehensive approaches including transcriptomics and lipidomics.

Results

Lipidomics analysis detected altered lipid profiles in the brains and synaptosomes of 5×FAD; nAbca7^-/- mice compared to controls. Transcriptomics profiling revealed that neuronal ABCA7 deficiency altered the expression of genes and pathways related to mitochondrial homeostasis and apoptosis, particularly in excitatory

SUBMITTER: Wang N 

PROVIDER: S-EPMC11947734 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature