Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy.
Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy.
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发表时间：
2006
期刊：
影响因子：
9.9
通讯作者：
M. Gurol;M. Irizarry;E. Smith;S. Raju;R. Diaz-Arrastia;T. Bottiglieri;J. Rosand;J. Growdon
中科院分区：
文献类型：
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作者：
M. Gurol;M. Irizarry;E. Smith;S. Raju;R. Diaz-Arrastia;T. Bottiglieri;J. Rosand;J. Growdon
微血管脑损伤是老年人认知障碍的一个重要因素，通常通过MRI上的白质高强度（WMH）程度来测量。最近的研究表明，循环β -淀粉样肽在微血管功能障碍和白质疾病中的作用。方法：作者对54例阿尔茨海默病（AD）或轻度认知障碍（AD/MCI）患者和42例脑淀粉样血管病（CAA）患者进行了与WMH相关的临床、生化和遗传因素的横断面研究。通过计算机辅助体积测量（归一化为颅内大小）来确定WMH的程度。生化测量包括通过特异性酶联免疫吸附法检测40和42个氨基酸的β -淀粉样蛋白（Abeta40和Abeta42）的血浆浓度。结果两组患者血浆Abeta40浓度与nWMH相关（AD/MCI组相关系数为0.48，CAA组相关系数为0.42,p < or = 0.005）。在调整了年龄、高血压、糖尿病、同型半胱氨酸、肌酐、叶酸、维生素B12和APOE基因型等潜在混杂因素后，血浆Abeta40仍与nWMH独立相关。在两组中，腔隙性梗死的存在也与Abeta40升高有关。CAA组nWMH （19.8 cm3）高于AD组（11.1 cm3）或MCI组（10.0 cm3），两组比较p < 0.05。结论：在阿尔茨海默病、轻度认知障碍或脑淀粉样血管病患者中，血浆β -淀粉样蛋白40浓度与白质高强度独立相关。如果在纵向研究中得到证实，这些数据将表明循环β -淀粉样肽是老年人这些常见疾病中微血管损伤的一种新的生物标志物或危险因素。
BACKGROUND Microvascular brain injury, typically measured by extent of white matter hyperintensity (WMH) on MRI, is an important contributor to cognitive impairment in the elderly. Recent studies suggest a role for circulating beta-amyloid peptide in microvascular dysfunction and white matter disease. METHODS The authors performed a cross-sectional study of clinical, biochemical, and genetic factors associated with WMH in 54 subjects with Alzheimer disease (AD) or mild cognitive impairment (AD/MCI) and an independent group of 42 subjects with cerebral amyloid angiopathy (CAA). Extent of WMH was determined by computer-assisted volumetric measurement normalized to intracranial size (nWMH). Biochemical measurements included plasma concentrations of the 40- and 42-amino acid species of beta-amyloid (Abeta40 and Abeta42) detected by specific enzyme-linked immunosorbent assays. RESULTS Plasma Abeta40 concentrations were associated with nWMH in both groups (correlation coefficient = 0.48 in AD/MCI, 0.42 in CAA, p < or = 0.005). Plasma Abeta40 remained independently associated with nWMH after adjustment for potential confounders among age, hypertension, diabetes, homocysteine, creatinine, folate, vitamin B12, and APOE genotype. The presence of lacunar infarctions was also associated with increased Abeta40 in both groups. nWMH was greater in CAA (19.8 cm3) than AD (11.1 cm3) or MCI (10.0 cm3; p < 0.05 for both comparisons). CONCLUSIONS Plasma beta-amyloid 40 concentration is independently associated with extent of white matter hyperintensity in subjects with Alzheimer disease, mild cognitive impairment, or cerebral amyloid angiopathy. If confirmed in longitudinal studies, these data would suggest circulating beta-amyloid peptide as a novel biomarker or risk factor for microvascular damage in these common diseases of the elderly.