Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, CA, USA.
Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, USA.
Neurobiol Aging. 2024 Dec;144:12-18. doi: 10.1016/j.neurobiolaging.2024.08.009. Epub 2024 Sep 3.
The amyloid beta (Aβ) 42/40 ratio has been widely studied as a biomarker in Alzheimer's disease (AD); however, other Aβ peptides could also represent relevant biomarkers. We measured levels of Aβ38/40/42 in plasma samples from cognitively-unimpaired older adults and determined the relationships between Aβ levels and amyloid positron-emission-tomography (PET) and performance on a learning and memory task. We found that all Aβ peptides individually and the Aβ42/40 ratio, but not the Aβ42/38 ratio, were significantly correlated with brain amyloid (Aβ-PET). Multiple linear modeling, adjusting for age, sex, education, APOE4 and Aβ-PET showed significant associations between the Aβ42/38 ratio and memory. Further, associations between the Aβ42/38 ratio and learning scores were stronger in males and in Aβ-PET-negative individuals. In contrast, no significant associations were detected between the Aβ42/40 ratio and any learning measure. These studies implicate the Aβ42/38 ratio as a biomarker to assess early memory deficits and underscore the utility of the Aβ38 fragment as an important biomarker in the AD field.
β 淀粉样蛋白 (Aβ) 42/40 比值已被广泛研究作为阿尔茨海默病 (AD) 的生物标志物；然而，其他 Aβ 肽也可能代表相关的生物标志物。我们测量了认知正常的老年人血浆样本中的 Aβ38/40/42 水平，并确定了 Aβ 水平与淀粉样蛋白正电子发射断层扫描 (PET) 和学习记忆任务表现之间的关系。我们发现，所有 Aβ 肽个体以及 Aβ42/40 比值，但不是 Aβ42/38 比值，与脑淀粉样蛋白 (Aβ-PET) 显著相关。多元线性模型，调整年龄、性别、教育、APOE4 和 Aβ-PET 后，Aβ42/38 比值与记忆之间存在显著关联。此外，Aβ42/38 比值与学习分数之间的关联在男性和 Aβ-PET 阴性个体中更强。相比之下，Aβ42/40 比值与任何学习测量均无显著关联。这些研究表明 Aβ42/38 比值可作为评估早期记忆缺陷的生物标志物，并强调 Aβ38 片段作为 AD 领域重要生物标志物的效用。
