title: Age-dependent effect of Alzheimer's risk variant of CLU on EEG alpha rhythm in non-demented adults.
abstract: 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 (Moretti etal., 2012a). 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.
authors.affiliation: Brain Research Department, Research Center of Neurology Russian Academy of Medical Science Moscow, Russia.
authors.forename: Natalya
authors.initials: N
authors.lastname: Ponomareva
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences Moscow, Russia ; Center of Brain Neurobiology and Neurogenetics, Institute of Cytogenetics and Genetics, Russian Academy of Sciences Novosibirsk, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Andreeva
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Protasova
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Lev
authors.initials: L
authors.lastname: Shagam
authors.affiliation: Brain Research Department, Research Center of Neurology Russian Academy of Medical Science Moscow, Russia.
authors.forename: Daria
authors.initials: D
authors.lastname: Malina
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Andrei
authors.initials: A
authors.lastname: Goltsov
authors.affiliation: Brain Research Department, Research Center of Neurology Russian Academy of Medical Science Moscow, Russia.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Fokin
authors.affiliation: Institute of Psychiatry Moscow, Russia.
authors.forename: Andrei
authors.initials: A
authors.lastname: Mitrofanov
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences Moscow, Russia ; Center of Brain Neurobiology and Neurogenetics, Institute of Cytogenetics and Genetics, Russian Academy of Sciences Novosibirsk, Russia ; University of Massachusetts Medical School, Department of Psychiatry, BNRI Worcester, MA, USA.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Rogaev
keywords: Alzheimer’s disease; EEG; aging; alpha rhythm; clusterin; genetic predisposition