Faculty of Health, Medicine and Life Sciences; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
Faculty of Health, Medicine and Life Sciences; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
Neurobiol Aging. 2021 Jun;102:17-22. doi: 10.1016/j.neurobiolaging.2021.01.024. Epub 2021 Feb 9.
Advanced Alzheimer's disease (AD) is characterized by higher noradrenaline metabolite levels that may be associated with AD pathology. The locus coeruleus (LC) is the main site for cerebral noradrenaline synthesis and LC volume loss occurs as early as Braak stage 1. This study investigates the association between noradrenergic turnover and brain morphology, and the modifying effect of AD pathology. The study sample included 77 memory clinic patients (37 cognitively unimpaired and 40 cognitively impaired (mild cognitive impairment or AD dementia)). Cortical thickness and volumetric analyses were performed using FreeSurfer. Cerebrospinal fluid was analyzed for noradrenergic metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), Aβ42 and phosphorylated tau. Higher MHPG was associated with lower cortical thickness and hippocampal volume at lower, but subthreshold, levels of Aβ42 and at higher p-tau levels. These associations remained significant after adding APOE-E4 or cognitive status as covariates. Our results suggest that greater MHPG together with worse AD pathology contributes to neurodegeneration, possibly before significant amyloidosis. The noradrenergic system may play an important role in early detection of AD-related processes.
阿尔茨海默病（AD）的高级阶段表现为去甲肾上腺素代谢物水平升高，这可能与 AD 病理有关。蓝斑（LC）是大脑去甲肾上腺素合成的主要部位，早在 Braak 1 期就会发生 LC 体积损失。本研究调查了去甲肾上腺素周转率与脑形态之间的关系，以及 AD 病理的修饰作用。研究样本包括 77 名记忆诊所患者（37 名认知正常和 40 名认知障碍（轻度认知障碍或 AD 痴呆））。使用 FreeSurfer 进行皮质厚度和体积分析。分析脑脊液中的去甲肾上腺素代谢物 3-甲氧基-4-羟基苯乙二醇（MHPG）、Aβ42 和磷酸化 tau。在 Aβ42 水平较低但低于阈值和 p-tau 水平较高时，较高的 MHPG 与皮质厚度和海马体积较低相关。在加入 APOE-E4 或认知状态作为协变量后，这些关联仍然显著。我们的研究结果表明，更高的 MHPG 加上更严重的 AD 病理可能会导致神经退行性变，这可能发生在明显淀粉样变性之前。去甲肾上腺素系统可能在 AD 相关过程的早期检测中发挥重要作用。
