Department of Psychiatry, New York University School of Medicine, Center of Excellence on Aging, Center for Brain Health, 145 East 32nd Street, 5th floor, New York, NY 10016, USA.
Neurobiol Aging. 2011 Dec;32(12):2131-41. doi: 10.1016/j.neurobiolaging.2009.12.026. Epub 2010 Feb 4.
Little is known whether cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) can predict both memory decline and associated longitudinal medial temporal lobe (MTL) gray matter (GM) reductions in cognitively healthy individuals. Fifty-seven normal elderly subjects received comprehensive evaluation at baseline and 2 years later. The baseline phosphorylated tau(231) (p-tau(231)), total tau, the amyloid beta (Aβ) Aβ42/Aβ40, t-tau/Aβ42 and p-tau(231)/Aβ42 ratios were examined as predictors of memory change and reductions in the global and MTL GM, determined from T1-weighted MRI. Twenty out of 57 participants experienced reduced memory performance at follow-up. The group with decreased memory performance showed higher baseline p-tau(231) (Z=-2.2, p=0.03), lower Aβ42/Aβ40 (t=-2.2 [55], p=0.04) and greater longitudinal MTL GM reductions (t([52])=-2.70, p=0.01). Higher baseline p-tau(231) was also associated with the absolute decrease in memory scores (rho=-0.30, p=0.02) and with longitudinal MTL GM reduction (F([2,52])=4.4, p=0.04, age corrected). Our results indicate that in normal individuals, elevated p-tau(231), a marker of neurofibrillary pathology is related to both a decrease in declarative memory and progressive atrophy of the MTL, suggesting its diagnostic potential in preclinical stage.
目前尚不清楚阿尔茨海默病（AD）的脑脊液（CSF）生物标志物是否可以预测认知健康个体的记忆下降和相关的纵向内侧颞叶（MTL）灰质（GM）减少。57 名正常老年人在基线和 2 年后接受了全面评估。基线磷酸化 tau(231)（p-tau(231)）、总 tau、淀粉样蛋白β（Aβ）Aβ42/Aβ40、t-tau/Aβ42 和 p-tau(231)/Aβ42 比值被检查为记忆变化和全球及 MTL GM 减少的预测指标，从 T1 加权 MRI 确定。20 名参与者在随访中记忆表现下降。记忆表现下降的组基线 p-tau(231)较高（Z=-2.2，p=0.03），Aβ42/Aβ40 较低（t=-2.2 [55]，p=0.04），纵向 MTL GM 减少较多（t([52])=-2.70，p=0.01）。基线 p-tau(231)也与记忆评分的绝对下降（rho=-0.30，p=0.02）和纵向 MTL GM 减少相关（F([2,52])=4.4，p=0.04，年龄校正）。我们的结果表明，在正常个体中，神经纤维病理学标志物 p-tau(231)升高与陈述性记忆下降和 MTL 进行性萎缩有关，表明其在临床前阶段具有诊断潜力。
