<i>PSEN1, PSEN2</i>, and <i>APP</i> mutations in 404 Chinese pedigrees with familial Alzheimer's disease
Longfei Jia, Yue Fu, Luxi Shen, Heng Zhang, Min Zhu, Qiongqiong Qiu, Qi Wang, Xin Yan, Chaojun Kong, Jing Hao, Cuibai Wei, Yi Tang, Wei Qin, Ying Li, Fen Wang, Dongmei Guo, Aihong Zhou, Xiumei Zuo, Yueyi Yu, Dan Li, Lina Zhao, Hongmei Jin, Jianping Jia
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.