Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
J Alzheimers Dis. 2023;92(1):81-93. doi: 10.3233/JAD-221100.
The primary manifestations of Alzheimer's disease (AD) include cognitive decline and brain gray matter volume (GMV) atrophy. Recent studies have found that plasma phosphorylated-tau (p-tau) concentrations perform better in diagnosing, differentiating, and monitoring the progression of AD. However, the correlation between plasma p-tau, GMV, and cognition remains unclear.
To investigate whether GMV plays a mediating role in the association between plasma p-tau concentrations and cognition.
In total, 99 participants (47 patients with AD and 52 cognitively unimpaired [CU] individuals) were included. All participants underwent neuropsychological assessments, laboratory examinations, and magnetic resonance imaging scans. Plasma p-tau217 and p-tau181 concentrations were measured using an enzyme-linked immunosorbent assay kit. Voxel-based morphometry was performed to assess participants' brain GMV. Partial correlation and mediation analyses were conducted in AD group.
Plasma p-tau concentrations were significantly higher in the AD group than in the CU group. Patients with AD had significant brain GMV atrophy in the right hippocampus, bilateral middle temporal gyrus, and right inferior temporal gyrus. In the AD group, there were significant correlations between plasma p-tau217 concentrations, GMV, and Mini-Mental State Examination (MMSE) scores. Brain GMV of the right hippocampus mediated the association between plasma p-tau217 concentrations and MMSE scores. A significant correlation between plasma p-tau181 and MMSE scores was not identified.
The findings indicate that p-tau217 is a promising biomarker for central processes affecting brain GMV and cognitive function. This may provide potential targets for future intervention and treatment of tau-targeting therapies in the early stages of AD.
阿尔茨海默病（AD）的主要表现包括认知能力下降和大脑灰质体积（GMV）萎缩。最近的研究发现，血浆磷酸化tau（p-tau）浓度在 AD 的诊断、鉴别和监测进展方面表现更好。然而，血浆 p-tau、GMV 和认知之间的相关性尚不清楚。
探讨 GMV 是否在血浆 p-tau 浓度与认知之间的关联中起中介作用。
共纳入 99 名参与者（47 名 AD 患者和 52 名认知正常[CU]个体）。所有参与者均接受神经心理学评估、实验室检查和磁共振成像扫描。采用酶联免疫吸附试验试剂盒检测血浆 p-tau217 和 p-tau181 浓度。采用基于体素的形态计量学评估参与者的脑 GMV。在 AD 组中进行偏相关和中介分析。
AD 组的血浆 p-tau 浓度显著高于 CU 组。AD 患者的右侧海马体、双侧颞中回和右侧颞下回的脑 GMV 明显萎缩。在 AD 组中，血浆 p-tau217 浓度与 GMV 及简易精神状态检查表（MMSE）评分之间存在显著相关性。右侧海马体 GMV 介导了血浆 p-tau217 浓度与 MMSE 评分之间的关联。血浆 p-tau181 与 MMSE 评分之间未发现显著相关性。
这些发现表明 p-tau217 是影响脑 GMV 和认知功能的中枢过程的有前途的生物标志物。这可能为未来 AD 早期针对 tau 的靶向治疗的干预和治疗提供潜在靶点。
