Аннотация:Motivation and Aim: Genetic predisposition and aging are the greatest known
risk factors for Alzheimer’s disease (AD). Clusterin (CLU) gene was identified to be
associated with AD in different populations, including Russian population (Harold et
al., 2009; Lambert et al., 2009; Golenkina et al., 2010). The prevalence of AD is higher
in women, but the mechanisms of the gender-related differences are not completely
understood. The normal brain undergoes a substantial decrease of functional connections
within resting-state networks during aging, but gender- and CLU-related differences in
functional connectivity remain unknown.
The present study aimed to determine the possible gender-related differences of the
alterations of brain functional connectivity in normal aging and to define the effect of
CLU genotype on theses alterations.
Methods and Algorithms: We examined age-related differences in resting state
functional connectivity assessed by interhemispheric EEG coherence in 157 non-demented
volunteers (age range 20-80 years), subdivided into subgroups of those younger and older
than 50 years of age and stratified by gender and CLU rs11136000 genotype. Informed
written consent was obtained from all participants. All subjects underwent a neurological
examination and cognitive screening. The significance of the differences between the logtransformed
EEG and parameters in different groups was estimated using ANOVA in the
general linear model (GLM). The analysis was adjusted for ApoE genotype.
Results: The older women showed decreased interhemispheric coherence values
compared to the younger women, while in the man age-dependent decrease of the
EEG coherence was significant only for beta coherence. In the women older than 50
years of age the presence of AD risk variant CLU CC was associated with lower alpha1
coherence. The reduction of alpha and beta interhemispheric coherence correlated with
the worse performance in Luria verbal memory test.
Conclusion: The results indicate that altered functional connectivity in normal aging
is associated with gender and CLU genotype. Progressive decline in interhemispheric
connectivity contributes to memory decrement and suggests the impact of age-related
disconnection process in pathogenesis of AD in women carrying AD risk variant CLU
CC. The results suggest that the neurophysiological markers may be important in
monitoring preclinical disease progression in at-risk elderly