The team of Professor Jianping Jia from Xuanwu Hospital reported 404 Chinese Alzheimer’s disease families for the first time in the world and revealed important genetic mechanisms

In January 2020, the team of Professor Jianping Jia from Xuanwu Hospital published an online article titled “PSEN1, PSEN2 and APP mutations in 404 Chinese pedigrees with familial Alzheimer’s disease” in Alzheimer’s & Dementia(IF: 14.423). The study conducted a 17-year follow-up study on 404 families with Familial Alzheimer’s disease (FAD) in China, and revealed the genetic rules of this disease in a thorough and systematic manner. This provides a theoretical basis for genetic intervention and gene therapy of AD in China.

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AD is a common disease in the elderly, but FAD is very rare. FAD integrates all the pathophysiological characteristics of AD disease and becomes the best population for studying pathogenesis. Since the first case of AD patients was reported in 1906, important pathogenesis such as Aβ theory, tau theory, inflammation theory, etc. have all come from the research of FAD. Therefore, research on AD needs to start with FAD.

Professor Jia Jianping’s team started to establish Chinese largest familial Alzheimer’s disease registration website (The Chinese Familial Alzheimer’s Disease Network,CFAN)(http://www.chinacfan.org/) in 2002 to collect FAD cases nationwide. As of September 2019, a total of 404 families and family members of more than 3,700 people have been collected. CFAN is currently the world’s largest FAD registration network. In this study, 50 PSENs/APP mutations were found (Figures 1, 2, 3), among which 11 mutations were reported for the first time in the world, indicating the heterogeneity of pathogenesis between Chinese and other races. Among 404 families, 83.17% of families do not carry mutations in the known gene PSENs/APP, and there are still a large number of unknown genes to be discovered. Such mining will have important implications for the discovery of the characteristic genes of Chinese AD.

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Figure.1 Distribution of amino acid substitutions in the PS1 proteins.
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Figure2. Distribution of amino acid substitutions in the PS2 proteins.
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Figure 3. Distribution of amino acid substitutions in the APP proteins.

Jia Jianping’s team reported the first case of FAD in China in 2005, which opened a precedent for the study of AD from genetics. After long-term systematic research, the mystery of Chinese familial AD gene mutations has been gradually revealed, which has had an important impact on understanding the pathogenesis of Chinese people’s AD, and has also provided ideas and platforms for Chinese AD genetic intervention and gene therapy. It is hopeful to start from the aspect of gene editing, reverse gene defects, and find a new breakthrough point for the ultimate cure of AD.

This study was supported by the Key Project of the National Natural Science Foundation of China (81530036); the National Key Scientific Instrument and Equipment Development Projects of China (31627803); Mission Program of Beijing Municipal Administration of Hospitals (SML20150801); Beijing Scholars Program; Beijing Brain Initiative from Beijing Municipal Science & Technology Commission (Z161100000216137); Innovation Base Training and Development Special Program (Z171100002217007); CHINA-CANADA Joint Initiative on Alzheimer’s Disease and Related Disorders (81261120571), and Project for Outstanding Doctor with Combined Ability ofWestern and Chinese Medicine.

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