Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
Neurobiol Aging. 2019 Dec;84:225-234. doi: 10.1016/j.neurobiolaging.2019.08.001. Epub 2019 Aug 9.
White matter hyperintensities (WMHs) are a common manifestation of cerebral small vessel disease. WMHs are also frequently observed in patients with familial and sporadic Alzheimer's disease, often with a particular posterior predominance. Whether amyloid and tau pathologies are linked to WMH occurrence is still debated. We examined whether cerebral amyloid and tau burden, reflected in cerebrospinal fluid amyloid-beta 1-42 (Aβ-42) and phosphorylated tau (p-tau), are related to WMH location in a cohort of 517 memory clinic patients. Two lesion mapping techniques were performed: voxel-based analyses and region of interest-based linear regression. Voxelwise associations were found between lower Aβ-42 and parieto-occipital periventricular WMHs. Regression analyses demonstrated that lower Aβ-42 correlated with larger WMH volumes in the splenium of the corpus callosum and posterior thalamic radiation, also after controlling for markers of vascular disease. P-tau was not consistently related to WMH occurrence. Our findings indicate that cerebral amyloid burden is associated with WMHs located in specific posterior white matter regions, possibly reflecting region-specific effects of amyloid pathology on the white matter.
脑白质高信号（WMHs）是脑小血管病的常见表现。WMHs 也常出现在家族性和散发性阿尔茨海默病患者中，常呈特定的后部优势分布。淀粉样蛋白和tau 病理学是否与 WMH 的发生有关仍存在争议。我们在一个 517 例记忆诊所患者的队列中研究了脑淀粉样蛋白和 tau 负担（反映在脑脊液淀粉样蛋白-β 1-42（Aβ-42）和磷酸化 tau（p-tau）中）与 WMH 位置的关系。进行了两种病变映射技术：体素分析和感兴趣区域的线性回归。发现较低的 Aβ-42 与顶枕叶脑室周围的 WMHs 之间存在体素相关性。回归分析表明，即使在控制血管疾病标志物后，较低的 Aβ-42 也与胼胝体压部和丘脑后辐射的 WMH 体积增大相关。p-tau 与 WMH 的发生并不一致相关。我们的研究结果表明，脑淀粉样蛋白负担与特定的后部白质WMHs 有关，可能反映了淀粉样蛋白病理学对白质的特定区域的影响。
