Department of Neurology, Erasmus Medical Center , Rotterdam, The Netherlands.
J Proteome Res. 2011 Nov 4;10(11):4902-10. doi: 10.1021/pr200270z. Epub 2011 Sep 28.
We have sought for disease-related proteins that could predict the onset of Alzheimer's disease (AD) in a study population derived from the Rotterdam Scan Study, a population-based prospective cohort study designed to investigate the etiology and natural history of age-related brain changes in the elderly. The serum proteome of 43 persons who developed AD, after an average of 4.2 years (±2.6 years SD) after blood sampling, and 43 gender- and age-matched controls who remained dementia-free during follow-up was investigated by liquid chromatography mass spectrometry. We identified 61 differentially expressed peptides between presymptomatic AD and controls, 9 of which were derived from pregnancy zone protein (PZP). Quantitative measurements using a multiple reaction monitoring assay showed a significant increase in concentration of PZP in presymptomatic AD (34.3 ± 20.6 mg/L) compared with controls (23.6 ± 13.6 mg/L) (p = 0.006). The difference in PZP was significant in women. Immunohistochemical validation of the findings on brain tissue sections showed strong PZP expression in senile plaques and in microglial and glial cells in AD with only low expression in some scattered glial cells in controls.
我们在一项源自鹿特丹扫描研究（一项基于人群的前瞻性队列研究，旨在研究老年人与年龄相关的大脑变化的病因和自然史）的研究人群中，寻找与疾病相关的蛋白质，以预测阿尔茨海默病（AD）的发病。在平均 4.2 年后（±2.6 年 SD）采血后，对 43 名发生 AD 的患者（平均年龄 77.3 岁）和 43 名性别和年龄匹配的在随访期间未出现痴呆的对照组的血清蛋白质组进行了液相色谱-质谱分析。我们在无症状 AD 患者和对照组之间鉴定出 61 个差异表达的肽，其中 9 个来自妊娠区蛋白（PZP）。使用多重反应监测测定法进行定量测量显示，无症状 AD 患者的 PZP 浓度明显升高（34.3 ± 20.6 mg/L），与对照组（23.6 ± 13.6 mg/L）相比（p = 0.006）。在女性中，PZP 的差异具有统计学意义。对脑组织切片的发现进行免疫组织化学验证显示，PZP 在 AD 的老年斑中和小胶质细胞和神经胶质细胞中表达强烈，而在对照组的一些散在神经胶质细胞中仅低表达。
