Generic placeholder image

Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Presenilin 1 and APP Gene Mutations in Early-Onset AD Families from a Southeast Region of China

Author(s): Jiajia Zhou, Yi Chen, Fanxia Meng, Kan Zhang, Xiaoyan Liu and Guoping Peng*

Volume 17, Issue 6, 2020

Page: [540 - 546] Pages: 7

DOI: 10.2174/1567205017666200624195809

Price: $65


Background: Early-Onset Familial Alzheimer’s Disease (EOFAD) has been reported to be associated with Presenilin 1 (PSEN1), Presenilin 2 (PSEN2), and Amyloid Precursor Protein (APP) genes. The spectrum of mutations in Chinese patients with EOFAD was rarely investigated.

Objective: To investigate the spectrum of mutations in patients with EOFAD in Chinese population.

Methods: We performed whole-exome sequencing and described relevant clinical features in a total of 67 subjects from 3 families with EOFAD.

Results: A splice mutation (p.S290C) in PSEN1 and a missense mutation (p.V717I) in APP were identified.

Conclusion: The variant p. S290C (c.869-2>G) in PSEN1 in Chinese EOAD family revealed different clinical phenotypes when compared with that of Europeans.

Keywords: Early-onset, familial, alzheimer's disease, presenilin 1, amyloid precursor protein, gene mutation, whole-exome sequencing.

Ridge PG, Ebbert MT, Kauwe JS. Genetics of Alzheimer’s disease. BioMed Res Int 2013; 2013 254954
[] [PMID: 23984328]
Zhu X-C, Tan L, Wang H-F, et al. Rate of early onset Alzheimer’s disease: A systematic review and meta-analysis. Ann Transl Med 2015; 3(3): 38.
[] [PMID: 25815299]
Wu L, Rosa-Neto P, Hsiung GY, et al. Early-onset familial Alzheimer’s disease (EOFAD). Can J Neurol Sci 2012; 39(4): 436-45.
[] [PMID: 22728850]
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34(7): 939-44.
[] [PMID: 6610841]
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol 1999; 56(3): 303-8.
[] [PMID: 10190820]
Shea YF, Chu LW, Chan AO, Ha J, Li Y, Song YQ. A systematic review of familial Alzheimer’s disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences. J Formos Med Assoc 2016; 115(2): 67-75.
[] [PMID: 26337232]
Bagyinszky E, Youn YC, An SS, Kim S. Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries. Clin Interv Aging 2016; 11: 1467-88.
[] [PMID: 27799753]
Vo VG, Bagyinszky E, Youn YC, An SSA, Kim S. APP, PSEN1, and PSEN2 mutations in asian patients with early-onset Alzheimer disease. Int J Mol Sci 2019; 20: 4757.
Ryan NS, Nicholas JM, Weston PSJ, et al. Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer’s disease: A case series. Lancet Neurol 2016; 15(13): 1326-35.
[] [PMID: 27777022]
Kowalska A, Pruchnik-Wolińska D, Florczak J, et al. Genetic study of familial cases of Alzheimer’s disease. Acta Biochim Pol 2004; 51(1): 245-52.
[] [PMID: 15094846]
Theuns J, Del-Favero J, Dermaut B, et al. Genetic variability in the regulatory region of presenilin 1 associated with risk for Alzheimer’s disease and variable expression. Hum Mol Genet 2000; 9(3): 325-31.
[] [PMID: 10655540]
Jiao B, Tang B, Liu X, et al. Mutational analysis in early-onset familial Alzheimer’s disease in Mainland China. Neurobiol Aging 2014; 35(8): 1957.e1-6.
[] [PMID: 24650794]
Jiang HY, Li GD, Dai SX, et al. Identification of PSEN1 mutations p.M233L and p.R352C in Han Chinese families with early-onset familial Alzheimer’s disease. Neurobiol Aging 2015; 36(3): 1602.e3-6.
[] [PMID: 25595498]
Rovelet-Lecrux A, Charbonnier C, Wallon D, et al. CNR-MAJ collaborators. De novo deleterious genetic variations target a biological network centered on Aβ peptide in early-onset Alzheimer disease. Mol Psychiatry 2015; 20(9): 1046-56.
[] [PMID: 26194182]
Blauwendraat C, Wilke C, Jansen IE, et al. Pilot whole-exome sequencing of a German early-onset Alzheimer’s disease cohort reveals a substantial frequency of PSEN2 variants. Neurobiol Aging 2016; 37: 208.e11-7.
[] [PMID: 26522186]
Perez-Tur J, Froelich S, Prihar G, et al. A mutation in Alzheimer’s disease destroying a splice acceptor site in the presenilin-1 gene. Neuroreport 1995; 7(1): 297-301.
[] [PMID: 8742474]
Steiner H, Romig H, Grim MG, et al. The biological and pathological function of the presenilin-1 Deltaexon 9 mutation is independent of its defect to undergo proteolytic processing. J Biol Chem 1999; 274(12): 7615-8.
[] [PMID: 10075646]
Lleó A, Blesa R, Queralt R, et al. Frequency of mutations in the presenilin and amyloid precursor protein genes in early-onset Alzheimer disease in Spain. Arch Neurol 2002; 59(11): 1759-63.
[] [PMID: 12433263]
Lan M-Y, Liu J-S, Wu Y-S, Peng CH, Chang YY. A novel APP mutation (D678H) in a Taiwanese patient exhibiting dementia and cerebral microvasculopathy. J Clin Neurosci 2014; 21(3): 513-5.
[] [PMID: 23931937]
Peng Xiang-Lei,, HouLei, Xu Shao-Hua, et al. Novel APP K724M mutation causes chinese early-onset familial alzheimer’s disease and increases amyloid-β42 to amyloid-β40 Ratio. Neurobiol Aging 2014; 35(11): 2657.e1-2657.e610.
Jiang B, Zhou J, Li H-L, et al. Mutation screening in Chinese patients with familial Alzheimer’s disease by whole-exome sequencing. Neurobiol Aging 2019; 76: 215.e15-21.
[] [PMID: 30598257]
Zhang G, Xie Y, Wang W, Feng X, Jia J. Clinical characterization of an APP mutation (V717I) in five Han Chinese families with early-onset Alzheimer’s disease. J Neurol Sci 2017; 372: 379-86.
[] [PMID: 27838006]
Guyant-Marechal I, Berger E, Laquerrière A, et al. Intrafamilial diversity of phenotype associated with app duplication. Neurology 2008; 71(23): 1925-6.
[] [PMID: 19047566]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy