Fagan Anne M, Mintun Mark A, Mach Robert H, Lee Sang-Yoon, Dence Carmen S, Shah Aarti R, LaRossa Gina N, Spinner Michael L, Klunk William E, Mathis Chester A, DeKosky Steven T, Morris John C, Holtzman David M
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ann Neurol. 2006 Mar;59(3):512-9. doi: 10.1002/ana.20730.
Amyloid-beta(42) (Abeta(42)) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Abeta(42) is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an Abeta(42) "sink," hindering transport of soluble Abeta(42) between brain and CSF. We investigated this hypothesis.
We compared the in vivo brain amyloid load (via positron emission tomography imaging of the amyloid-binding agent, Pittsburgh Compound-B [PIB]) with CSF Abeta(42) and other measures (via enzyme-linked immunosorbent assay) in clinically characterized research subjects.
Subjects fell into two nonoverlapping groups: those with positive PIB binding had the lowest CSF Abeta(42) level, and those with negative PIB binding had the highest CSF Abeta(42) level. No relation was observed between PIB binding and CSF Abeta(40), tau, phospho-tau(181), plasma Abeta(40), or plasma Abeta(42). Importantly, PIB binding and CSF Abeta(42) did not consistently correspond with clinical diagnosis; three cognitively normal subjects were PIB-positive with low CSF Abeta(42), suggesting the presence of amyloid in the absence of cognitive impairment (ie, preclinical AD).
These observations suggest that brain amyloid deposition results in low CSF Abeta(42), and that amyloid imaging and CSF Abeta(42) may potentially serve as antecedent biomarkers of (preclinical) AD.
β淀粉样蛋白（42）（Aβ（42））似乎在阿尔茨海默病（AD）发病机制中起核心作用，并且是淀粉样斑块的主要成分。阿尔茨海默型痴呆患者的平均脑脊液（CSF）Aβ（42）水平降低。这种降低可能反映了斑块作为Aβ（42）的“汇”，阻碍了可溶性Aβ（42）在脑和脑脊液之间的运输。我们对这一假设进行了研究。
我们在具有临床特征的研究对象中，比较了体内脑淀粉样蛋白负荷（通过淀粉样蛋白结合剂匹兹堡化合物-B [PIB]的正电子发射断层扫描成像）与CSF Aβ（42）及其他指标（通过酶联免疫吸附测定）。
研究对象分为两个不重叠的组：PIB结合阳性的患者CSF Aβ（42）水平最低，PIB结合阴性的患者CSF Aβ（42）水平最高。未观察到PIB结合与CSF Aβ（40）、tau、磷酸化tau（181）蛋白、血浆Aβ（40）或血浆Aβ（42）之间存在关联。重要的是，PIB结合和CSF Aβ（42）与临床诊断并不一致；三名认知正常的受试者PIB呈阳性但CSF Aβ（42）水平较低，提示在无认知障碍的情况下存在淀粉样蛋白（即临床前AD）。
这些观察结果表明脑淀粉样蛋白沉积导致CSF Aβ（42）水平降低，并且淀粉样蛋白成像和CSF Aβ（42）可能潜在地作为（临床前）AD的先行生物标志物。
