Accession PRJCA005593
Title ACAA1 in Alzheimer's disease
Relevance Medical
Data types Transcriptome or Gene expression
Organisms Homo sapiens
Description Alzheimer's disease (AD) is characterized by synaptic failure, dendritic and axonal atrophy, neuronal death and progressive loss of cognitive function. Pathogenic mutations in known AD causal genes such as APP, PSEN1 and PSEN2 impair a variety of pathways including protein processing, axonal transport, and metabolic homeostasis. Here, we identified a missense variant rs117916664 (c.896T>C, p.Asn299Ser [p.N299S]) of the acetyl-CoA acyltransferase 1 (ACAA1) gene in a Han Chinese AD family by whole genome sequencing, and validated its association with early-onset familial AD in an independent cohort. Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity, impairing lysosomal function, and aggravating the Aβ pathology and neuronal loss, which finally caused cognitive impairment in a murine model. Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.
Sample scope Monoisolate
Release date 2021-06-24
Grants
Agency program Grant ID Grant title
National Natural Science Foundation of China (NSFC) 31730037
National Natural Science Foundation of China (NSFC) 31900737
National Natural Science Foundation of China (NSFC) 82022017
Submitter Rongcan    Luo  (luorongcan@mail.kiz.ac.cn)
Organization Kunming Institute of Zoology, Chinese Academy of Sciences
Submission date 2021-06-24

Project Data

Resource name Description
BioSample (26)  show -