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Identification and characterization of variants in PSEN1, PSEN2, and APP genes in Chinese patients with early-onset Alzheimer's disease

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收录情况： ◇ SCIE

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机构： [1]Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China. [2]Advanced Innovation Center for Human Brain Protection, the National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. [3]The Experimental High School Attached to Beijing Normal University, Beijing, 100080, China.

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关键词： Alzheimer’s disease EOAD Amyloid β APP PSEN1 PSEN2

摘要：

Variants in PSEN1, PSEN2, and APP are major genetic causes of early-onset Alzheimer's disease (EOAD). Our study aimed to identify the genotypic and phenotypic spectrums in a Chinese EOAD cohort and confirm their pathogenicity by functional analysis. This study included 304 unrelated clinically diagnosed EOAD participants of Chinese Han ancestry. Whole-exome sequencing revealed that 26 out of 304 individuals (8.6%) carried rare variants in PSEN1, PSEN2, and APP, including 16 in PSEN1 (5.3%), 6 in PSEN2 (2.0%), and 4 in APP (1.3%). Eight variants were novel, including PSEN1 p.Q56R, PSEN1 p.L174P, PSEN1 p.S289P, PSEN1 p.Y466C, PSEN2 p.R17W, PSEN2 p.F331Y, APP p.D197N, and APP p.D252V. Functional study revealed that the PS1 L174P, S289P, R377M, Y466C, PS2 V214L, and M239T mutants increased Aβ42 levels and Aβ42/Aβ40 ratios. The PS1 L174P, R377M, and Y466C mutants decreased the maturation of presenilin-1. Our findings highlight the prevalence and pathogenic significance of APP /PSENs variants in a Chinese EOAD cohort and expand the phenotypic and genotypic spectrum of EOAD.© 2025. The Author(s).

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出版当年[2025]版：

大类 | 1 区

医学

小类 | 1 区临床神经病学 1 区神经科学

最新[2025]版：

大类 | 1 区

医学

小类 | 1 区临床神经病学 1 区神经科学

JCR分区：

出版当年[2023]版：

Q1 CLINICAL NEUROLOGY Q1 NEUROSCIENCES

最新[2024]版：

Q1 CLINICAL NEUROLOGY Q1 NEUROSCIENCES

影响因子： 7.6 最新[2024版] 8.8 最新五年平均 8 出版当年[2023版] 8.3 出版当年五年平均 9 出版前一年[2022版] 7.6 出版后一年[2024版]

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第一作者机构： [1]Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

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