title: Novel APP K724M mutation causes Chinese early-onset familial Alzheimer's disease and increases amyloid-β42 to amyloid-β40 ratio.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly individuals. Although there are several million cases of AD estimated in China with the most population in the world, no Chinese early-onset familial AD caused by new APP gene mutation has ever been reported. Here, we first described a Chinese family with early-onset AD that was inherited in autosomal dominant manner, and the age of onset was 46.6 ± 7.7 years (n = 5; range, 40-58 years). By using genetic analysis of 3 collected patients' DNA samples, we identified a heterozygous APP gene mutation (g.275363A>T, K724M according to APP770). Finally, when APP695 with K724M mutation was ectopically expressed in HEK293 cell, the ratio of amyloid-β42 to amyloid-β40 was 2.23-fold higher than that of wild-type control. Together, our data suggest that APP K724M gene mutation may contribute to the cause of this Chinese early-onset familial AD.
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Xiang-Lei
authors.initials: XL
authors.lastname: Peng
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Xu
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Zhou
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Yan-Peng
authors.initials: YP
authors.lastname: Zheng
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Yuan-Hui
authors.initials: YH
authors.lastname: Fu
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Zhang
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R. China. Electronic address: gxt-137@medmail.com.cn.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Guan
authors.affiliation: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China. Electronic address: jshhe@bjtu.edu.cn.
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Amyloid precursor protein; Amyloid-beta; Early-onset familial Alzheimer's disease; K724M; Mutation