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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease
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Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease

机译：外周Aβ亚种是阿尔茨海默氏病的危险生物标志物

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摘要

Plasma A/342 and Aβ40 levels are putative biomarkers for Alzheimer's disease (AD), but their significance and predictive value have been inconclusive. In AD transgenic models, plasma and cerebro-spinal fluid levels of A/342 and A/340 increase with age but subsequently decrease when Aβ begins to accumulate in brain and with the onset of cognitive impairment. To determine the predictive value of Aβ levels in elderly populations, we investigated how plasma Aβ42, A/340, and a protofibrillar subspecies of Aβ42 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 Aβ42 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 Aβ42, a decreased Aβ42/Aβ40 ratio and, with the onset of cognitive impairment, decreased protofibrillar Aβ42 levels. Our results suggest individuals with elevated plasma Aβ42 are at increased risk of AD and that with the onset of disease, the decline in some forms of Aβ may reflect compartmentalization of Aβ peptides in the brain.
机译：血浆A / 342和Aβ40水平是阿尔茨海默氏病（AD）的假定生物标志物，但它们的意义和预测价值尚无定论。在AD转基因模型中，A / 342和A / 340的血浆和脑脊髓液水平随年龄增加而增加，但随后随着Aβ开始在脑中积累和认知障碍的发作而降低。为了确定老年人群中Aβ水平的预测价值，我们调查了血浆Aβ42，A / 340和Aβ42的原纤维亚种如何随时间以及认知障碍或AD的发作而变化。在1125名无痴呆症的老年人中，104名参与者（9.2％）在4.6年的随访中发展为AD。研究开始时较高的血浆Aβ42水平与AD风险增加了三倍有关。然而，向AD的转化伴随着血浆Aβ42的显着下降，Aβ42/Aβ40比的降低以及伴随认知障碍的发作，原纤维Aβ42水平的降低。我们的结果表明，血浆Aβ42升高的个体罹患AD的风险增加，并且随着疾病的发作，某些形式的Aβ的下降可能反映了Aβ肽在大脑中的分隔。

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