Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease

Ying Gao; Ru-Jing Ren; Zi-Lin Zhong; Eric Dammer; Qian-Hua Zhao; Shan Shan; Zheng Zhou; Xia Li; Yue-Qi Zhang; Hai-Lun Cui; Yong-Bo Hu; Sheng-Di Chen; Jian-Jun Chen; Qi-Hao Guo; Gang Wang

doi:10.1016/j.neurobiolaging.2019.01.018

Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease

Neurobiol Aging. 2019 May:77:154-157. doi: 10.1016/j.neurobiolaging.2019.01.018. Epub 2019 Jan 31.

Authors

Ying Gao¹, Ru-Jing Ren¹, Zi-Lin Zhong², Eric Dammer³, Qian-Hua Zhao⁴, Shan Shan⁵, Zheng Zhou⁵, Xia Li⁶, Yue-Qi Zhang¹, Hai-Lun Cui¹, Yong-Bo Hu¹, Sheng-Di Chen¹, Jian-Jun Chen⁷, Qi-Hao Guo⁸, Gang Wang⁹

Affiliations

¹ Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Tenth People's Hospital & Department of Medical Genetics, Tongji University School of Medicine, Shanghai, China.
³ Department of Biochemistry, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.
⁴ Department of Neurology & Institute of Neurology, Huashan Hospital, Fudan University, WHO Collaborating Center for Research and Training in Neurosciences, Shanghai, China.
⁵ National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
⁶ Alzheimer's Disease and Related Disorders Center, Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ Shanghai Tenth People's Hospital & Department of Medical Genetics, Tongji University School of Medicine, Shanghai, China. Electronic address: [email protected].
⁸ Department of Neurology & Institute of Neurology, Huashan Hospital, Fudan University, WHO Collaborating Center for Research and Training in Neurosciences, Shanghai, China. Electronic address: [email protected].
⁹ Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].

PMID: 30822634
DOI: 10.1016/j.neurobiolaging.2019.01.018

Abstract

Causative mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) account for a majority of cases of familial Alzheimer disease (FAD) inherited in an autosomal-dominant pattern. For the sake of characterizing mutations, index patients from 148 families with FAD were enrolled from mainland China. Sanger sequencing of the genes APP, PSEN1, and PSEN2 was performed to characterize the mutation spectrum of the Chinese population. Thirteen of 148 (8.8%) individuals had possible pathogenic APP, PSEN1, or PSEN2 variants, including 2 (15.4%) APP variants, 8 (61.5%) PSEN1 variants, and 3 (23.1%) PSEN2 variants. PSEN1 variants represented the largest proportion in Chinese FAD, and PSEN2 variants are responsible for late-onset FAD in China. Analysis of genetic-clinical correlations permitted the conclusion that FAD phenotypes were mainly influenced by specific genetic defects.

Keywords: APP; Familial Alzheimer’s disease; Mutation; PSEN1; PSEN2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Alzheimer Disease / genetics*
Amyloid beta-Protein Precursor / genetics*
Asian People / genetics
Female
Genes, Dominant
Genetic Association Studies
Humans
Male
Middle Aged
Mutation*
Phenotype
Presenilin-1 / genetics*
Presenilin-2 / genetics*

Substances

Amyloid beta-Protein Precursor
PSEN1 protein, human
PSEN2 protein, human
Presenilin-1
Presenilin-2