区域脑白质高信号与认知正常和轻度认知障碍老年人的阿尔茨海默病生物标志物。
Regional White Matter Hyperintensities and Alzheimer's Disease Biomarkers Among Older Adults with Normal Cognition and Mild Cognitive Impairment.
机构信息
Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
J Alzheimers Dis. 2023;92(1):323-339. doi: 10.3233/JAD-220846.
BACKGROUND
Alzheimer's disease (AD) frequently co-occurs with other brain pathologies. Recent studies suggest there may be a mechanistic link between AD and small vessel cerebrovascular disease (CVD), as opposed to simply the overlap of two disorders.
OBJECTIVE
We investigated the cross-sectional relationship between white matter hyperintensity (WMH) volumes (markers of CVD) and cerebrospinal fluid (CSF) biomarkers of AD.
METHODS
WMH volumes were assessed globally and regionally (i.e., frontal, parietal, temporal, occipital, and limbic). CSF AD biomarkers (i.e., Aβ 40, Aβ 42, Aβ 42/Aβ 40 ratio, phosphorylated tau-181 [p-tau181], and total tau [t-tau]) were measured among 152 non-demented individuals (134 cognitively unimpaired and 18 with mild cognitive impairment (MCI)).
RESULTS
Linear regression models showed that among all subjects, higher temporal WHM volumes were associated with AD biomarkers (higher levels of p-tau181, t-tau, and Aβ 40), particularly among APOE ɛ 4 carriers (independent of Aβ 42 levels). Higher vascular risk scores were associated with greater parietal and frontal WMH volumes (independent of CSF AD biomarker levels). Among subjects with MCI only, parietal WMH volumes were associated with a lower level of Aβ 42/Aβ 40. In addition, there was an association between higher global WMH volumes and higher CSF t-tau levels among younger participants versus older ones (∼<65 versus 65+ years), independent of Aβ 42/Aβ 40 and p-tau181.
CONCLUSION
These findings suggest that although WMH are primarily related to systemic vascular risk and neurodegeneration (i.e., t-tau), AD-specific pathways may contribute to the formation of WMH in a regionally-specific manner, with neurofibrillary tangles (i.e., p-tau) playing a role in temporal WMHs and amyloid (i.e., Aβ 42/Aβ 40) in parietal WMHs.
背景
阿尔茨海默病（AD）常与其他脑部病变同时发生。最近的研究表明，AD 与小血管脑血管疾病（CVD）之间可能存在一种机制联系，而不是两种疾病的简单重叠。
目的
我们研究了脑白质高信号（WMH）体积（CVD 的标志物）与 AD 脑脊液（CSF）生物标志物之间的横断面关系。
方法
对全球和区域（即额叶、顶叶、颞叶、枕叶和边缘叶）WMH 体积进行评估。在 152 名非痴呆个体（134 名认知正常和 18 名轻度认知障碍（MCI））中测量 CSF AD 生物标志物（即 Aβ 40、Aβ 42、Aβ 42/Aβ 40 比值、磷酸化 tau-181 [p-tau181]和总 tau [t-tau]）。
结果
线性回归模型显示，在所有受试者中，较高的颞叶 WMH 体积与 AD 生物标志物（p-tau181、t-tau 和 Aβ 40 水平较高）相关，特别是在 APOE ɛ 4 携带者中（与 Aβ 42 水平无关）。较高的血管风险评分与更大的顶叶和额叶 WMH 体积相关（与 CSF AD 生物标志物水平无关）。仅在 MCI 患者中，顶叶 WMH 体积与 Aβ 42/Aβ 40 水平较低相关。此外，在较年轻的参与者（约 <65 岁与 65 岁以上）中，较高的全球 WMH 体积与较高的 CSF t-tau 水平相关，而与 Aβ 42/Aβ 40 和 p-tau181 无关。
结论
这些发现表明，尽管 WMH 主要与系统性血管风险和神经退行性变（即 t-tau）有关，但 AD 特定途径可能以区域特异性方式导致 WMH 的形成，神经原纤维缠结（即 p-tau）在颞叶 WMH 中起作用，淀粉样蛋白（即 Aβ 42/Aβ 40）在顶叶 WMH 中起作用。
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