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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Screening for Genetic Mutations Associated with Early-Onset Alzheimer’s Disease in Han Chinese

Author(s): Cuicui Liu, Lin Cong, Min Zhu, Yongxiang Wang, Shi Tang, Xiaojuan Han, Qinghua Zhang, Na Tian, Keke Liu, Xiaoyan Liang, Wenxin Fa, Nan Wang, Tingting Hou* and Yifeng Du*

Volume 19, Issue 10, 2022

Published on: 21 November, 2022

Page: [724 - 733] Pages: 10

DOI: 10.2174/1567205020666221028112915

Price: $65


Background: Early-onset Alzheimer’s disease (EOAD) is highly influenced by genetic factors. Numerous mutations in amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN1 and PSEN2) have been identified for EOAD, but they can only account for a small proportion of EOAD cases.

Objective: This study aimed to screen genetic mutations and variants associated with EOAD among Han Chinese adults.

Methods: This study included 34 patients with EOAD and 26 controls from a population-based study and neurological ward. We first sequenced mutations in APP/PSENs and then performed whole-exome sequencing in the remaining patients with negative mutations in APP/PSENs to screen for additional potential genetic variants. Among patients who were negative in genetic screening tests, we further evaluated the risk burden of genes related to the Aβ metabolism-centered network to search for other probable causes of EOAD.

Results: We identified 7 functional variants in APP/PSENs in 8 patients, including 1 APP mutation (p. Val715Met), 3 PSEN1 mutations (p. Phe177Ser; p. Arg377Met; p. Ile416Thr), and 3 PSEN2 mutations (p. Glu24Lys; p. Gly34Ser; p. Met239Thr). Of the remaining 26 EOAD cases without mutations in APP/PSENs, the proportion of carrying rare variants of genes involved in Aβ and APP metabolism was significantly higher than that of controls (84.6% vs. 73.1%, P=0.042). Thirty-one risk genes with 47 variants were identified in 22 patients. However, in 26 normal subjects, only 20 risk genes with 29 variants were identified in 19 subjects.

Conclusions: Our findings demonstrate the role of APP/PSENs mutations in EOAD, identifying a new PSEN2 missense mutation, and further offer valuable insights into the potential genetic mechanisms of EOAD without APP/PSENs mutations among Han Chinese.

Keywords: Early-onset Alzheimer’s disease, genetic mutations, whole-exome sequencing, Aβ-centered network, neurology, genetic variants.

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