AUTHOR=Liu Yingzi , Xiao Xuewen , Liu Hui , Liao Xinxin , Zhou Yafang , Weng Ling , Zhou Lu , Liu Xixi , Bi Xiang-yun , Xu Tianyan , Zhu Yuan , Yang Qijie , Zhang Sizhe , Hao Xiaoli , Zhang Weiwei , Wang Junling , Jiao Bin , Shen Lu TITLE=Clinical characteristics and genotype-phenotype correlation analysis of familial Alzheimer’s disease patients with pathogenic/likely pathogenic amyloid protein precursor mutations JOURNAL=Frontiers in Aging Neuroscience VOLUME=14 YEAR=2022 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.1013295 DOI=10.3389/fnagi.2022.1013295 ISSN=1663-4365 ABSTRACT=

Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with aging, environmental, and genetic factors. Amyloid protein precursor (APP) is a known pathogenic gene for familial Alzheimer’s disease (FAD), and now more than 70 APP mutations have been reported, but the genotype-phenotype correlation remains unclear. In this study, we collected clinical data from patients carrying APP mutations defined as pathogenic/likely pathogenic according to the American college of medical genetics and genomics (ACMG) guidelines. Then, we reanalyzed the clinical characteristics and identified genotype-phenotype correlations in APP mutations. Our results indicated that the clinical phenotypes of APP mutations are generally consistent with typical AD despite the fact that they show more non-demented symptoms and neurological symptoms. We also performed genotype-phenotype analysis according to the difference in APP processing caused by the mutations, and we found that there were indeed differences in onset age, behavioral and psychological disorders of dementia (BPSD) and myoclonus.