title: Genotype (cystatin C) and EEG phenotype in Alzheimer disease and mild cognitive impairment: a multicentric study.
abstract: Previous findings demonstrated that haplotype B of CST3, the gene coding for cystatin C, is a recessive risk factor for late-onset Alzheimer's disease (AD; Finckh, U., von der Kammer, H., Velden, J., Michel, T., Andresen, B., Deng, A., Zhang, J., Muller-Thomsen, T., Zuchowski, K., Menzer, G., Mann, U., Papassotiropoulos, A., Heun, R., Zurdel, J., Holst, F., Benussi, L., Stoppe, G., Reiss, J., Miserez, A.R., Staehelin, H.B., Rebeck, G.W., Hyman, B.T., Binetti, G., Hock, C., Growdon, J.H., Nitsch, R.M., 2000. Genetic association of the cystatin C gene with late-onset Alzheimer disease. Arch. Neurol. 57, 1579-1583). In the present multicentric electroencephalographic (EEG) study, we analyzed the effects of CST3 haplotypes on resting cortical rhythmicity in subjects with AD and mild cognitive impairment (MCI) with the hypothesis that sources of resting EEG rhythms are more impaired in carriers of the CST3 B haplotype than non-carriers. We enrolled a population of 84 MCI subjects (42% with the B haplotype) and 65 AD patients (40% with the B haplotype). Resting eyes-closed EEG data were recorded in all subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Results showed that the amplitude of alpha 1 (parietal, occipital, temporal areas) and alpha 2 (occipital area) was statistically lower in CST3 B carriers than non-carriers (P < 0.01). Whereas there was a trend towards statistical significance that amplitude of occipital delta sources was stronger in CST3 B carriers than in non-carriers. This was true for both MCI and AD subjects. The present findings represent the first demonstration of relationships between the AD genetic risk factor CST3 B and global neurophysiological phenotype (i.e., cortical delta and alpha rhythmicity) in MCI and AD subjects, prompting future genotype-EEG phenotype studies for the early prediction of AD conversion in individual MCI subjects.
authors.affiliation: Dip. Fisiologia Umana e Farmacologia, Univ. La Sapienza Rome, Italy. claudio.babiloni@uniroma1.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Babiloni
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.forename: Gabriella
authors.initials: G
authors.lastname: Busonero
authors.forename: Simona
authors.initials: S
authors.lastname: Cesaretti
authors.forename: Gloria
authors.initials: G
authors.lastname: Dal Forno
authors.forename: Claudio
authors.initials: C
authors.lastname: Del Percio
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Frisoni
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.forename: Guido
authors.initials: G
authors.lastname: Rodriguez
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Rossini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000523:psychology; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics*; D004569:Electroencephalography; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins