Subthreshold Amyloid Predicts Tau Deposition in Aging
Subthreshold Amyloid Predicts Tau Deposition in Aging
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DOI：
10.1523/jneurosci.0485-18.2018
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发表时间：
2018-05-09
影响因子：
5.3
通讯作者：
Jagust, William J.
中科院分区：
文献类型：
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作者：
Leal, Stephanie L.;Lockhart, Samuel N.;Jagust, William J.
目前早期检测阿尔茨海默病（AD）的方法依赖于将个体分类为与β -淀粉样蛋白（A β）核心病理相关的生物标志物“阳性”或“阴性”。然而，A β的积累开始缓慢，在生物标志物变得异常之前的几年。我们使用纵向[C-11]匹兹堡化合物B PET扫描和神经心理学评估来研究阿尔茨海默病病理的早期变化及其如何影响认知正常的老年人（N = 71，平均年龄75岁，35%男性）的记忆。我们在观察期结束时使用[F-18] AV-1451 PET扫描来测量我们样本子集（N = 37）的后续tau沉积。我们发现无症状老年人基线A β水平和A β斜率之间呈倒u型关系的证据，表明即使在认知正常的成年人中，A β积累也会减慢。在名义上为淀粉样蛋白阴性的参与者中，淀粉样蛋白积累率和A β的基线水平都预测了与AD相关的皮层Braak区域的早期tau沉积。淀粉样蛋白测量仅对A β基线水平升高时的记忆衰退敏感，这表明在影响记忆之前就发生了病理性积累。这些发现支持早期干预淀粉样蛋白降低治疗的必要性，即使对那些淀粉样蛋白阴性的人也是如此。
Current approaches to the early detection of Alzheimer's disease (AD) rely upon classifying individuals as "positive" or "negative" for biomarkers related to the core pathology of beta-amyloid (A beta). However, the accumulation of A beta begins slowly, years before biomarkers become abnormal. We used longitudinal [C-11] Pittsburgh Compound B PET scanning and neuropsychological assessment to investigate the earliest changes in AD pathology and how it affects memory in cognitively normal older humans (N = 71; mean age 75 years; 35% male). We used [F-18] AV-1451 PET scanning at the end of the observation period to measure subsequent tau deposition in a subset of our sample (N = 37). We found evidence for an inverted-U relationship between baseline A beta levels and A beta slope in asymptomatic older adults, suggesting a slowing of A beta accumulation even in cognitively normal adults. In participants who were nominally amyloid negative, both the rate of amyloid accumulation and the baseline levels of A beta predicted early tau deposition in cortical Braak regions associated with AD. Amyloid measures were only sensitive to memory decline as baseline levels of A beta increased, suggesting that pathological accumulation occurs before impacting memory. These findings support the necessity of early intervention with amyloid-lowering therapies even in those who are amyloid negative.