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.
Highlights
Alzheimer’s disease (AD) is the major cause of dementia in the elderly
Subjects were evaluated with the mini-mental state examination (MMSE) and Clinical Dementia Rating (CDR) scale (Hughes et al, 1982)
The homozygous presence of the AD risk variant CLU CC in non-demented subjects was associated with an increase of alpha3 and to a lesser, though significant, extent of alpha1 power in the subjects older than 50 years of age
Summary
Alzheimer’s disease (AD) is the major cause of dementia in the elderly. It is estimated that 35.6 million people worldwide currently suffer from dementia, with the prevalence projected to increase to 65.7 million by 2030 and 115.4 million by 2050. Alzheimer’s disease has a strong genetic basis with heritability estimates of up to 80% (Gatz et al, 2006). A common polymorphism in the apolipoprotein E gene (ApoE), located on chromosome 19, has been established as the most common genetic risk factor for AD in Caucasian ethnic groups, including the Russian population (Saunders et al, 1993; Schmechel et al, 1993; Farrer et al, 1997; Rogaev, 1999)
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