Age-dependent effect of Alzheimer's risk variant of CLU on EEG alpha rhythm in non-demented adults.
Age-dependent effect of Alzheimer's risk variant of CLU on EEG alpha rhythm in non-demented adults.
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DOI：
10.3389/fnagi.2013.00086
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发表时间：
2013
影响因子：
4.8
通讯作者：
Rogaev E
中科院分区：
文献类型：
--
作者：
Ponomareva N;Andreeva T;Protasova M;Shagam L;Malina D;Goltsov A;Fokin V;Mitrofanov A;Rogaev E
携带CLU基因（rs 11136000）的基因组区域的多态性与阿尔茨海默病（AD）的风险相关。CLU C等位基因被认为是AD的危险因素，而T等位基因可能具有保护作用。我们研究了AD相关CLU基因型对非痴呆成年人大脑活动（静息态α节律活动）的常见神经生理学特征的影响，并阐明了这种影响是否会随着年龄的增长而改变。我们研究了一组非痴呆个体（年龄范围20-80岁）的定量脑电图（EEG），分为年轻（年龄范围20-50岁）和老年（年龄范围51-80岁）队列，并按CLU多态性分层。为了排除载脂蛋白E（ApoE）基因型对EEG特征的影响，仅将不含ApoE ε4等位基因的受试者纳入研究。非痴呆受试者中AD风险变体CLU CC的纯合子存在与α 3绝对功率的增加相关。此外，CLU基因型对α 3的影响在50岁以上的受试者中更高。该研究还显示了α地形分布的年龄依赖性改变，其发生独立于CLU基因型。轻度认知障碍患者的上α功率增加与海马萎缩相关。在我们的研究中，CLU CC-依赖性增加上α节律，特别是在老年非痴呆个体中增强，可能意味着基因型与衰老中海马神经生理学的临床前失调有关，并且该因素可能有助于AD的发病机制。
Polymorphism in the genomic region harboring the CLU gene (rs11136000) has been associated with the risk for Alzheimer’s disease (AD). CLU C allele is assumed to confer risk for AD and the allele T may have a protective effect. We investigated the influence of the AD-associated CLU genotype on a common neurophysiological trait of brain activity (resting-state alpha-rhythm activity) in non-demented adults and elucidated whether this influence is modified over the course of aging. We examined quantitative electroencephalography (EEG) in a cohort of non-demented individuals (age range 20–80) divided into young (age range 20–50) and old (age range 51–80) cohorts and stratified by CLU polymorphism. To rule out the effect of the apolipoprotein E (ApoE) genotype on EEG characteristics, only subjects without the ApoE ε4 allele were included in the study. The homozygous presence of the AD risk variant CLU CC in non-demented subjects was associated with an increase of alpha3 absolute power. Moreover, the influence of CLU genotype on alpha3 was found to be higher in the subjects older than 50 years of age. The study also showed age-dependent alterations of alpha topographic distribution that occur independently of the CLU genotype. The increase of upper alpha power has been associated with hippocampal atrophy in patients with mild cognitive impairment. In our study, the CLU CC-dependent increase in upper alpha rhythm, particularly enhanced in elderly non-demented individuals, may imply that the genotype is related to preclinical dysregulation of hippocampal neurophysiology in aging and that this factor may contribute to the pathogenesis of AD.
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影响因子：
4.3
作者：
de Haan W;Mott K;van Straaten EC;Scheltens P;Stam CJ
通讯作者：
Stam CJ
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
4
作者：
Babiloni, Claudio;Lizio, Roberta;Frisoni, Giovanni B.
通讯作者：
Frisoni, Giovanni B.
DOI：
10.1523/jneurosci.5794-10.2011
发表时间：
2011-05-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Braskie MN;Jahanshad N;Stein JL;Barysheva M;McMahon KL;de Zubicaray GI;Martin NG;Wright MJ;Ringman JM;Toga AW;Thompson PM
通讯作者：
Thompson PM
影响因子：
4.7
作者：
Chiang, A. K. I.;Rennie, C. J.;Kerr, C. C.
通讯作者：
Kerr, C. C.