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A rare variant in MLKL confers susceptibility to ApoE ɛ4-negative Alzheimer's disease in Hong Kong Chinese population
Wang B.3; Bao S.1; Zhang Z.1; Zhou X.1; Wang J.3; Fan Y.1; Zhang Y.1; Li Y.11; Chen L.1; Jia Y.1; Li J.1; Li M.8; Zheng W.9; Mu N.2; Wang L.1; Yu Z.1; Wong D.S.M.1; Zhang Y.1; Kwan J.1; Ka-Fung Mak H.1; Ambalavanan A.10; Zhou S.10; Cai W.4; Zheng J.13; Huang S.6; Rouleau G.A.10; Yang W.1; Rogaeva E.12; Ma X.3; St George-Hyslop P.12; Chu L.W.1; Song Y.-Q.1
2018-08-01
Source PublicationNeurobiology of Aging
ISSN15581497 01974580
Volume68Pages:160.e1-160.e7
Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. To identify rare genetic factors other than apolipoprotein E ɛ4 allele (ApoE ɛ4) contributing to the pathogenesis of late-onset AD (LOAD), we conducted a whole-exome analysis of 246 ApoE ɛ4-negative LOAD cases and 172 matched controls in Hong Kong Chinese population. LOAD patients showed a significantly higher burden of rare loss-of-function variants in genes related to immune function than healthy controls. Among the genes involved in immune function, we identified a rare stop-gain variant (p.Q48X) in mixed lineage kinase domain like pseudokinase (MLKL) gene present exclusively in 6 LOAD cases. MLKL is expressed in neurons, and the its expression levels in the p.Q48X carriers were significantly lower than that in age-matched wild-type controls. The ratio of Aβ42 to Aβ40 significantly increased in MLKL knockdown cells compared to scramble controls. MLKL loss-of-function mutation might contribute to late-onset ApoE ɛ4-negative AD in the Hong Kong Chinese population.

KeywordApoe Ɛ4-negative Late-onset Alzheimer's Disease Mlkl Whole Exome Sequencing
DOI10.1016/j.neurobiolaging.2018.03.006
URLView the original
Indexed BySCI
WOS Research AreaGeriatrics & Gerontology ; Neurosciences & Neurology
WOS SubjectGeriatrics & Gerontology ; Neurosciences
WOS IDWOS:000434462100021
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.The University of Hong Kong
2.Guangzhou Brain Hospital
3.National Research Institute for Family Planning, Beijing
4.Hainan Medical University
5.Cambridge Institute for Medical Research
6.West China Hospital of Sichuan University
7.Peking Union Medical College
8.Sun Yat-Sen University, Zhongshan School of Medicine
9.Universidade de Macau
10.McGill University, Montreal Neurological Institute and Hospital
11.Qilu University of Technology
12.University of Toronto
13.East China University of Science and Technology
Recommended Citation
GB/T 7714
Wang B.,Bao S.,Zhang Z.,et al. A rare variant in MLKL confers susceptibility to ApoE ɛ4-negative Alzheimer's disease in Hong Kong Chinese population[J]. Neurobiology of Aging,2018,68:160.e1-160.e7.
APA Wang B..,Bao S..,Zhang Z..,Zhou X..,Wang J..,...&Song Y.-Q..(2018).A rare variant in MLKL confers susceptibility to ApoE ɛ4-negative Alzheimer's disease in Hong Kong Chinese population.Neurobiology of Aging,68,160.e1-160.e7.
MLA Wang B.,et al."A rare variant in MLKL confers susceptibility to ApoE ɛ4-negative Alzheimer's disease in Hong Kong Chinese population".Neurobiology of Aging 68(2018):160.e1-160.e7.
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