Department of Neurodegeneration, University of Tuebingen, Germany.
J Alzheimers Dis. 2010;19(3):937-42. doi: 10.3233/JAD-2010-1289.
A large proportion of demented Lewy body disease patients have Alzheimer's disease (AD)- like pathology, in particular amyloid-beta (Abeta) plaques. Cystatin C (CysC) is a carrier of soluble Abeta (42) in the cerebrospinal fluid (CSF) and reduces Abeta plaque formation. The CST3 BB genotype leads to a reduced secretion of the protein in vitro and increases the risk for AD, suggesting that variability in the CST3 gene and CysC protein concentration may be associated with dementia in Lewy body disease. We therefore determined the CST3 genotype in 51 demented and 71 nondemented Lewy body disease patients, and in 52 controls, as well as CSF CysC and Abeta (42) levels from 132 of these subjects. The CST3 BB genotype was associated with lowered CSF CysC levels and with dementia. Demented Lewy body disease patients had decreased CSF CysC levels. The correlation between CSF CysC and Abeta (42) levels was high in non-demented subjects, but poor in demented patients. We conclude that, in Lewy body disease, the CST3 BB genotype and low CSF CysC levels are associated with dementia, possibly through a disturbed elimination of soluble Abeta(42).
路易体痴呆患者中有很大一部分存在阿尔茨海默病（AD）样病理学，特别是淀粉样蛋白-β（Abeta）斑块。半胱氨酸蛋白酶抑制剂 C（CysC）是脑脊液（CSF）中可溶性 Abeta（42）的载体，可减少 Abeta 斑块形成。CST3 BB 基因型导致体外蛋白分泌减少，并增加 AD 的风险，表明 CST3 基因和 CysC 蛋白浓度的变异性可能与路易体病中的痴呆有关。因此，我们确定了 51 名痴呆和 71 名非痴呆路易体病患者以及 52 名对照者的 CST3 基因型，以及其中 132 名受试者的 CSF CysC 和 Abeta（42）水平。CST3 BB 基因型与 CSF CysC 水平降低和痴呆有关。痴呆路易体病患者的 CSF CysC 水平降低。非痴呆患者 CSF CysC 与 Abeta（42）水平之间的相关性很高，但痴呆患者的相关性很差。我们得出结论，在路易体病中，CST3 BB 基因型和低 CSF CysC 水平与痴呆有关，可能通过对可溶性 Abeta（42）的清除障碍。
