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
Dip. Fisiologia Umana e Farmacologia, Univ. La Sapienza Rome, Italy.
Neuroimage. 2006 Feb 1;29(3):948-64. doi: 10.1016/j.neuroimage.2005.08.030. Epub 2005 Oct 6.
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.
先前的研究结果表明，编码胱抑素C的CST3基因的单倍型B是晚发性阿尔茨海默病（AD）的隐性风险因素（芬克，U.，冯·德·卡默，H.，费尔登，J.，米歇尔，T.，安德烈森，B.，邓，A.，张，J.，米勒 - 托姆森，T.，祖乔夫斯基，K.，门泽尔，G.，曼，U.，帕帕索蒂罗普洛斯，A.，霍恩，R.，祖德尔，J.，霍尔斯特，F.，贝努西，L.，斯托佩，G.，赖斯，J.，米塞雷兹，A.R.，施泰林，H.B.，雷贝克，G.W.，海曼，B.T.，比内蒂，G.，霍克，C.，格罗登，J.H.，尼奇，R.M.，2000年。胱抑素C基因与晚发性阿尔茨海默病的遗传关联。《神经病学档案》57，1579 - 1583）。在本项多中心脑电图（EEG）研究中，我们分析了CST3单倍型对AD和轻度认知障碍（MCI）患者静息皮质节律性的影响，假设是CST3 B单倍型携带者的静息EEG节律来源比非携带者受损更严重。我们招募了84名MCI受试者（42%携带B单倍型）和65名AD患者（40%携带B单倍型）。记录了所有受试者闭眼静息状态下的EEG数据。感兴趣的EEG节律有δ波（2 - 4赫兹）、θ波（4 - 8赫兹）、α1波（8 - 10.5赫兹）、α2波（10.5 - 13赫兹）、β1波（13 - 20赫兹）和β2波（20 - 30赫兹）。通过低分辨率脑电磁断层扫描（LORETA）估计EEG皮质源。结果显示，CST3 B携带者的α1波（顶叶、枕叶、颞叶区域）和α2波（枕叶区域）振幅在统计学上低于非携带者（P < 0.01）。而枕叶δ波源的振幅在CST3 B携带者中比非携带者更强，这有统计学意义的趋势。MCI和AD受试者均如此。本研究结果首次证明了AD遗传风险因素CST3 B与MCI和AD受试者的整体神经生理表型（即皮质δ波和α波节律性）之间的关系，促使未来进行基因型 - EEG表型研究以早期预测个体MCI受试者向AD的转化。
