Neuronal ABCA7 deficiency aggravates mitochondrial dysfunction and neurodegeneration in Alzheimer's disease DOI Creative Commons
Ni Wang,

Yining Pan,

Skylar C Starling

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Abstract INTRODUCTION Loss‐of‐function variants of the ABCA7 gene are associated with an increased risk Alzheimer's disease (AD). How neuronal contributes to AD pathogenesis is unknown. METHODS Using neuron‐specific Abca7 KO mice (n −/− ) or without 5×FAD amyloid model background and post mortem brains, we investigated AD‐related phenotypes through comprehensive approaches including transcriptomics lipidomics. RESULTS Lipidomics analysis detected altered lipid profiles in brains synaptosomes 5×FAD; n compared controls. Transcriptomics profiling revealed that deficiency expression genes pathways related mitochondrial homeostasis apoptosis, particularly excitatory neurons. Consistently, isolated from showed diminished mitochondria respiration reduced synaptic protein levels, which further supported by results human brains. DISCUSSION Our findings reveal plays a critical role important for function survival presence pathology. Highlights Neuronal exacerbates Aβ pathology damage mice. alters brain transcriptomes lipidomes disturbs functions associates

Language: Английский

Neuronal ABCA7 deficiency aggravates mitochondrial dysfunction and neurodegeneration in Alzheimer's disease DOI Creative Commons
Ni Wang,

Yining Pan,

Skylar C Starling

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Abstract INTRODUCTION Loss‐of‐function variants of the ABCA7 gene are associated with an increased risk Alzheimer's disease (AD). How neuronal contributes to AD pathogenesis is unknown. METHODS Using neuron‐specific Abca7 KO mice (n −/− ) or without 5×FAD amyloid model background and post mortem brains, we investigated AD‐related phenotypes through comprehensive approaches including transcriptomics lipidomics. RESULTS Lipidomics analysis detected altered lipid profiles in brains synaptosomes 5×FAD; n compared controls. Transcriptomics profiling revealed that deficiency expression genes pathways related mitochondrial homeostasis apoptosis, particularly excitatory neurons. Consistently, isolated from showed diminished mitochondria respiration reduced synaptic protein levels, which further supported by results human brains. DISCUSSION Our findings reveal plays a critical role important for function survival presence pathology. Highlights Neuronal exacerbates Aβ pathology damage mice. alters brain transcriptomes lipidomes disturbs functions associates

Language: Английский

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