Genotype (cystatin C) and EEG phenotype in Alzheimer disease and mild cognitive impairment: A multicentric study

Claudio Babiloni, Luisa Benussi, Giuliano Binetti, Paolo Bosco, Gabriella Busonero, Simona Cesaretti, Gloria Dal Forno, Claudio Del Percio, Raffaele Ferri, Giovanni Frisoni, Roberta Ghidoni, Guido Rodriguez, Rosanna Squitti, Paolo M. Rossini

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)948-964
Number of pages17
JournalNeuroImage
Volume29
Issue number3
DOIs
Publication statusPublished - Feb 1 2006

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Cystatin C
Haplotypes
Alzheimer Disease
Genotype
Phenotype
Periodicity
Animal Tarsus
Electromagnetic Phenomena
Genes
Tomography
Cognitive Dysfunction
Brain
Population

Keywords

  • Alzheimer's disease (AD)
  • Brain rhythms
  • Cystatin C
  • Electroencephalography (EEG)
  • Low-resolution brain electromagnetic tomography (LORETA)
  • Mild cognitive impairment (MCI)

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

Cite this

Genotype (cystatin C) and EEG phenotype in Alzheimer disease and mild cognitive impairment : A multicentric study. / Babiloni, Claudio; Benussi, Luisa; Binetti, Giuliano; Bosco, Paolo; Busonero, Gabriella; Cesaretti, Simona; Dal Forno, Gloria; Del Percio, Claudio; Ferri, Raffaele; Frisoni, Giovanni; Ghidoni, Roberta; Rodriguez, Guido; Squitti, Rosanna; Rossini, Paolo M.

In: NeuroImage, Vol. 29, No. 3, 01.02.2006, p. 948-964.

Research output: Contribution to journalArticle

Babiloni, Claudio ; Benussi, Luisa ; Binetti, Giuliano ; Bosco, Paolo ; Busonero, Gabriella ; Cesaretti, Simona ; Dal Forno, Gloria ; Del Percio, Claudio ; Ferri, Raffaele ; Frisoni, Giovanni ; Ghidoni, Roberta ; Rodriguez, Guido ; Squitti, Rosanna ; Rossini, Paolo M. / Genotype (cystatin C) and EEG phenotype in Alzheimer disease and mild cognitive impairment : A multicentric study. In: NeuroImage. 2006 ; Vol. 29, No. 3. pp. 948-964.
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T1 - Genotype (cystatin C) and EEG phenotype in Alzheimer disease and mild cognitive impairment

T2 - A multicentric study

AU - Babiloni, Claudio

AU - Benussi, Luisa

AU - Binetti, Giuliano

AU - Bosco, Paolo

AU - Busonero, Gabriella

AU - Cesaretti, Simona

AU - Dal Forno, Gloria

AU - Del Percio, Claudio

AU - Ferri, Raffaele

AU - Frisoni, Giovanni

AU - Ghidoni, Roberta

AU - Rodriguez, Guido

AU - Squitti, Rosanna

AU - Rossini, Paolo M.

PY - 2006/2/1

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N2 - 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.

AB - 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.

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KW - Brain rhythms

KW - Cystatin C

KW - Electroencephalography (EEG)

KW - Low-resolution brain electromagnetic tomography (LORETA)

KW - Mild cognitive impairment (MCI)

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