Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease
Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease
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DOI：
10.1073/pnas.0805902105
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发表时间：
2008-09-16
影响因子：
11.1
通讯作者：
Mayeux, Richard
中科院分区：
文献类型：
--
作者：
Schupf, Nicole;Tang, Ming X.;Mayeux, Richard
血浆A β 42和A β 40水平是阿尔茨海默病（AD）的推定生物标志物，但其意义和预测价值尚无定论。在AD转基因模型中，A β 42和A β 40的血浆和脑脊液水平随着年龄的增长而增加，但随后当A β开始在大脑中积聚时以及随着认知障碍的发作而降低。为了确定A β水平在老年人群中的预测价值，我们研究了血浆A β 42、A β 40和A β 42的原纤维亚种如何随时间和认知障碍或AD的发作而变化。在一个由1,125名无痴呆症的老年人组成的队列中，104名（9.2%）参与者在4.6年的随访中患上了AD。研究开始时较高的血浆A β 42水平与AD风险增加3倍相关。然而，转换为AD伴随着血浆A β 42的显著下降，A β 42/A β 40比值降低，并且随着认知障碍的发作，A β 42水平降低。我们的研究结果表明，血浆A β 42升高的个体患AD的风险增加，并且随着疾病的发作，某些形式的A β下降可能反映了大脑中A β肽的区室化。
Plasma A beta 42 and A beta 40 levels are putative biomarkers for Alzheimer's disease (AD), but their significance and predictive value have been inconclusive. In AD transgenic models, plasma and cerebrospinal fluid levels of A beta 42 and A beta 40 increase with age but subsequently decrease when A beta begins to accumulate in brain and with the onset of cognitive impairment. To determine the predictive value of A beta levels in elderly populations, we investigated how plasma A beta 42, A beta 40, and a protofibrillar subspecies of A beta 42 changed over time and with the onset of cognitive impairment or AD. In a cohort of 1,125 elderly persons without dementia, 104 (9.2%) of the participants developed AD over 4.6 years of follow-up. Higher plasma A beta 42 levels at the onset of the study were associated with a threefold increased risk of AD. However, conversion to AD was accompanied by a significant decline in plasma A beta 42, a decreased A beta 42/A beta 40 ratio and, with the onset of cognitive impairment, decreased protofibrillar A beta 42 levels. Our results suggest individuals with elevated plasma A beta 42 are at increased risk of AD and that with the onset of disease, the decline in some forms of A beta may reflect compartmentalization of A beta peptides in the brain.