Associations among locus coeruleus catecholamines, tau pathology, and memory in aging
Associations among locus coeruleus catecholamines, tau pathology, and memory in aging
复制标题
DOI：
10.1038/s41386-022-01269-6
复制
发表时间：
2022-01-15
影响因子：
7.6
通讯作者：
Berry, Anne S.
中科院分区：
文献类型：
--
作者：
Ciampa, Claire J.;Parent, Jourdan H.;Berry, Anne S.
蓝斑(LC)是大脑神经调节剂去甲肾上腺素的主要来源，也极易受到阿尔茨海默病(AD)相关tau病理的影响。去甲肾上腺素在神经保护功能中发挥作用，可能会减缓AD的进展，也是最佳记忆表现的基础。成功地维持LC神经化学功能代表了一种防止AD相关病理传播的候选机制，并可能促进尽管有病理变化的记忆表现的保存。使用[F-18]间酪氨酸([F-18]FMT)PET成像测量LC感兴趣区的儿茶酚胺合成能力，我们研究了认知正常的老年人(n=49)LC神经化学功能、AD相关病理和记忆表现之间的关系。参与者分别接受了[C-11]匹兹堡化合物B和[F-18]Flortaucipir PET，以量化β-淀粉样蛋白(n=49)和tau负荷(n=42)。在有大量β-淀粉样蛋白的个体中，较高的LC[F-18]FMT净示踪剂内流(Ki(Vis))与较低的颞部tau相关。在我们样本的一个子集(n=30)中的纵向tau-PET分析支持这些发现，揭示了在较高LC[F-18]FMT KI(Vis)的背景下，时间tau累积减少。较高的LC儿茶酚胺合成能力与自我报告的认知投入和一生中的体力活动呈正相关，这是用终身经历问卷衡量的成功衰老的预测因素。LC儿茶酚胺合成能力减缓了tau对记忆的负面影响，因此，在考虑到tau负担的情况下，较高的LC儿茶酚胺合成能力与比预期更好的记忆表现有关。这些PET发现提供了对AD脆弱性和活着的人脑中认知弹性的神经化学机制的洞察。
The locus coeruleus (LC) is the brain's major source of the neuromodulator norepinephrine, and is also profoundly vulnerable to the development of Alzheimer's disease (AD)-related tau pathology. Norepinephrine plays a role in neuroprotective functions that may reduce AD progression, and also underlies optimal memory performance. Successful maintenance of LC neurochemical function represents a candidate mechanism of protection against the propagation of AD-related pathology and may facilitate the preservation of memory performance despite pathology. Using [F-18]Fluoro-m-tyrosine ([F-18]FMT) PET imaging to measure catecholamine synthesis capacity in LC regions of interest, we examined relationships among LC neurochemical function, AD-related pathology, and memory performance in cognitively normal older adults (n = 49). Participants underwent [C-11]Pittsburgh compound B and [F-18]Flortaucipir PET to quantify beta-amyloid (n = 49) and tau burden (n = 42) respectively. In individuals with substantial beta-amyloid, higher LC [F-18]FMT net tracer influx (Ki(vis)) was associated with lower temporal tau. Longitudinal tau-PET analyses in a subset of our sample (n = 30) support these findings to reveal reduced temporal tau accumulation in the context of higher LC [F-18]FMT Ki(vis). Higher LC catecholamine synthesis capacity was positively correlated with self-reported cognitive engagement and physical activity across the lifespan, established predictors of successful aging measured with the Lifetime Experiences Questionnaire. LC catecholamine synthesis capacity moderated tau's negative effect on memory, such that higher LC catecholamine synthesis capacity was associated with better-than-expected memory performance given an individual's tau burden. These PET findings provide insight into the neurochemical mechanisms of AD vulnerability and cognitive resilience in the living human brain.