Center of Excellence on Aging, Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA.
Neurobiol Aging. 2012 Jul;33(7):1215-27. doi: 10.1016/j.neurobiolaging.2011.02.012. Epub 2011 May 6.
It is not well known whether Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers are associated with brain damage in cognitively normal elderly. The combined influence of CSF biomarkers and hypertension (HTN) on the gray matter (GM) is also not well described. One hundred fifteen cognitively healthy subjects (mean age 62.6 ± 9.5%, 62% women) received clinical assessment, a high resolution magnetic resonance imaging (MRI), and a lumbar puncture. The CSF levels of total tau (t-tau), hyperphosphorylated tau (p-tau(231)), amyloid beta (Aβ42/Aβ40), p-tau(231)/Aβ42, and t-tau/Aβ42 were dichotomized as "high" and "low" based on accepted cut off values. Statistical parametric mapping was used to examine MRI scans for regional GM density, studied as a function of the CSF markers, HTN, and combination of both. Global and medial temporal lobe (MTL) GM was also assessed. Voxel based morphometry revealed that higher t-tau was associated with lower GM density in the precunei. Subjects with higher p-tau(231) and p-tau(231)/Aβ42 had less GM in temporal lobes. Low Aβ42/Aβ40 was related to less GM in the thalami, caudate, and midbrain. Subjects with hypertension showed more GM atrophy in the cerebellum, occipital, and frontal regions. Simultaneous presence of elevated CSF AD biomarkers and HTN was associated with more GM atrophy than either marker individually, but no interaction effects were identified. In conclusion, in normal elderly CSF tau markers were associated predominantly with lower GM estimates in structures typically affected early in the AD process. In this presymptomatic stage when no cognitive impairment is present, AD biomarkers and HTN have additive effects on gray matter damage.
目前尚不清楚阿尔茨海默病（AD）脑脊液（CSF）生物标志物是否与认知正常的老年人的脑损伤有关。CSF 生物标志物和高血压（HTN）对灰质（GM）的综合影响也描述得不够清楚。115 名认知健康的受试者（平均年龄 62.6±9.5%，62%为女性）接受了临床评估、高分辨率磁共振成像（MRI）和腰椎穿刺。脑脊液中总 tau（t-tau）、磷酸化 tau（p-tau（231））、淀粉样蛋白β（Aβ42/Aβ40）、p-tau（231）/Aβ42 和 t-tau/Aβ42 的水平根据公认的截断值被分为“高”和“低”。使用统计参数映射检查 MRI 扫描的区域性 GM 密度，研究其作为 CSF 标志物、HTN 和两者结合的函数。还评估了全脑和内侧颞叶（MTL）GM。基于体素的形态计量学显示，较高的 t-tau 与后扣带回 GM 密度降低有关。较高的 p-tau（231）和 p-tau（231）/Aβ42 与颞叶 GM 减少有关。低 Aβ42/Aβ40 与丘脑、尾状核和中脑 GM 减少有关。高血压患者小脑、枕叶和额叶 GM 萎缩更为明显。同时存在升高的 CSF AD 生物标志物和 HTN 与单独任何一种标志物相比，GM 萎缩更为明显，但未发现交互作用。总之，在正常老年人中，CSF tau 标志物主要与 AD 过程中早期受影响的结构中的 GM 估计值较低有关。在没有认知障碍的这个无症状阶段，AD 生物标志物和 HTN 对灰质损伤有相加作用。
