Longfei Jia1, Yue Fu1, Luxi Shen1, Heng Zhang1, Min Zhu1, Qiongqiong Qiu1, Qi Wang1, Xin Yan1, Chaojun Kong1, Jing Hao1, Cuibai Wei1, Yi Tang1, Wei Qin1, Ying Li1, Fen Wang1, Dongmei Guo1, Aihong Zhou1, Xiumei Zuo1, Yueyi Yu1, Dan Li1, Lina Zhao1, Hongmei Jin1, Jianping Jia1,2,3,4,5,6. 1. Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China. 2. Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. 3. Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China. 4. Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China. 5. Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China. 6. National Clinical Research Center for Geriatric Disorders, Beijing, China.
Abstract
INTRODUCTION: The PSENs/APP mutation distribution in Chinese patients with familial Alzheimer's disease (FAD) remains unclear. We aimed to analyze the genetic features of Chinese FAD pedigrees with and without PSENs/APP mutations. METHODS: In total, 1330 patients with Alzheimer's disease (AD) or mild cognitive impairment in 404 pedigrees were enrolled from the Chinese Familial Alzheimer's Disease Network. PSENs/APP mutations and APOE frequencies were determined. RESULTS: In total, 13.12% of pedigrees carried PSENs/APP missense mutations, 3.71% carried PSENs/APP synonymous/untranslated region variants, and 83.17% did not carry PSENs/APP mutations. Eleven missense mutations were first identified. In patients without PSENs/APP mutations, 44.31% carried one APOEε4 allele, and 14.85% two APOEε4 alleles. DISCUSSION: The new PSENs/APP mutations indicate heterogeneity in AD pathogenesis between Chinese and other ethnic groups. The low mutation rate suggests the involvement of other genes/factors in Chinese FAD. APOEε4 might be a major gene for some FAD without PSENs/APP mutations.
INTRODUCTION: The PSENs/APP mutation distribution in Chinese patients with familial Alzheimer's disease (FAD) remains unclear. We aimed to analyze the genetic features of Chinese FAD pedigrees with and without PSENs/APP mutations. METHODS: In total, 1330 patients with Alzheimer's disease (AD) or mild cognitive impairment in 404 pedigrees were enrolled from the Chinese Familial Alzheimer's Disease Network. PSENs/APP mutations and APOE frequencies were determined. RESULTS: In total, 13.12% of pedigrees carried PSENs/APP missense mutations, 3.71% carried PSENs/APP synonymous/untranslated region variants, and 83.17% did not carry PSENs/APP mutations. Eleven missense mutations were first identified. In patients without PSENs/APP mutations, 44.31% carried one APOEε4 allele, and 14.85% two APOEε4 alleles. DISCUSSION: The new PSENs/APP mutations indicate heterogeneity in AD pathogenesis between Chinese and other ethnic groups. The low mutation rate suggests the involvement of other genes/factors in Chinese FAD. APOEε4 might be a major gene for some FAD without PSENs/APP mutations.