A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-beta pathology and cognitive decline

KIZ OpenIR > 科研部门 > 疾病机理遗传学和进化医学学科组（姚永刚）

	A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-beta pathology and cognitive decline
	Luo, RC; Fan, Y; Yang, J; Ye, MS; Zhang, DF; Guo, K; Li, X; Bi, R; Xu, M; Yang, LX; Li, Y; Ran, XQ; Jiang, HY; Zhang, C; Tan, LW; Sheng, NY; Yao, YG
	2021
发表期刊	SIGNAL TRANSDUCTION AND TARGETED THERAPY
ISSN	2095-9907
卷号	6 期号:1
摘要	Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction, neuronal death, and brain atrophy, with amyloid-beta (A beta) plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue, which all lead to loss of cognitive function. Pathogenic mutations in the well-known AD causal genes including 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 A beta 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.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13490
专题	科研部门_疾病机理遗传学和进化医学学科组（姚永刚）昆明动物研究所
推荐引用方式 GB/T 7714	Luo, RC,Fan, Y,Yang, J,et al. A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-beta pathology and cognitive decline[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2021,6(1).
APA	Luo, RC.,Fan, Y.,Yang, J.,Ye, MS.,Zhang, DF.,...&Yao, YG.(2021).A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-beta pathology and cognitive decline.SIGNAL TRANSDUCTION AND TARGETED THERAPY,6(1).
MLA	Luo, RC,et al."A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-beta pathology and cognitive decline".SIGNAL TRANSDUCTION AND TARGETED THERAPY 6.1(2021).

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