Cortical tau load is associated with white matter hyperintensities
Cortical tau load is associated with white matter hyperintensities
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DOI：
10.1186/s40478-015-0240-0
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发表时间：
2015-09-30
影响因子：
7.1
通讯作者：
Attems, Johannes
中科院分区：
文献类型：
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作者：
McAleese, Kirsty E.;Firbank, Michael;Attems, Johannes
简介：脑白色病变（WML），在12加权MRI上显示为白色高信号（WMH），包括脑白色（WM）的结构损伤和完整性丧失，通常被认为与小血管疾病（SVD）相关。然而，已经提出WM损伤也可能是继发于皮质阿尔茨海默病（AD）病理学的退行性轴突损失的结果，即，过度磷酸化的tau（HPT）和淀粉d-β（A）。在这里，我们调查的影响HPT，A13和SVD对WIVIH severity.Results：36人死后右固定大脑半球（平均年龄84.4 - 7.7岁;男性：16，女性：20）含有不同量的AD病理（AD：23，对照：13）进行T2加权MRI与WIVIH评估根据年龄相关的白色物质变化量表（ARWMC）。解剖后，使用来自右半球额叶、颞叶、顶叶和枕叶区域的组织样本，我们通过测量A18免疫反应性（HPT-IR）和4G 8免疫反应性（A β-IR）覆盖的百分比面积来定量评估皮质HPT和A β病理负荷，并通过计算WM动脉/小动脉的scratchet指数（SI）来评估WM SVD的严重程度。将HPT-IR、A β-IR和SI与ARWMC评分进行比较。与对照组相比，AD病例的HPT-β R和WM ARWMC评分均显著较高，而两组之间的SI值相似。ARWMC分数与HPT-IR，A β-IR和SI在各个地区，然而，线性回归显示，只有HPT-IR是一个显着的独立预测ARWMC scores.Conclusions：在这里，我们已经表明，增加皮质HPT负担独立预测的严重程度WMH表明其潜在的重要作用，在发病机制的WM损害。此外，我们的研究结果表明，在AD患者中，WMH的存在可能表明皮质AD相关的病理，而不是SVD。进一步的研究是必要的，以阐明导致WM损伤的病理过程，并澄清WMH是否可以作为皮质AD相关病理学的一般生物标志物。
Introduction: Cerebral white matter lesions (WML), visualized as white matter hyperintensities (WMH) on 12-weighted MRI, encompass structural damage and loss of integrity of the cerebral white matter (WM) and are commonly assumed to be associated with small vessel disease (SVD). However, it has been suggested that WM damage may also be the result of degenerative axonal loss that is secondary to cortical Alzheimer's disease (AD) pathologies i.e., hyperphosphorylated tau (HPT) and amylo d-beta (A). Here we investigate the influence of HPT, A13 and SVD on WIVIH severity.Results: 36 human post-mortem right fixed cerebral hemispheres (mean age 84.4 7.7 years; male: 16, female: 20) containing varying amounts of AD-pathology (AD: 23, controls: 13) underwent T2- weighted MRI with WIVIH assessed according to the age related white matter change scale (ARWMC). After dissection, using tissue samples from the frontal, temporal, parietal and occipital regions from the right hemisphere, we quantitatively assessed cortical HPT and A beta pathology burden by measuring the percentage area covered by A18 immunoreactivity (HPT-IR) and 4G8 immunoreactivity (A beta-IR), and assessed the severity of WM SVD by calculating the sclerotic index (SI) of WM arteries/arterioles. HPT-IR, A beta-IR, and SI were compared with ARWMC scores. HPT-beta R, and WM ARWMC scores were all significantly higher in AD cases compared to controls, while SI values were similar between groups. ARWMC scores correlated with HPT-IR, A beta-IR and SI in various regions, however, linear regression revealed that only HPT-IR was a significant independent predictor of ARWMC scores.Conclusions: Here we have shown that increasing cortical HPT burden independently predicted the severity of WMH indicating its potentially important role in the pathogenesis of WM damage. Moreover, our findings suggest that in AD patients the presence of WMH may indicate cortical AD-associated pathology rather than SVD. Further studies are warranted to elucidate the pathological processes that lead to WM damage and to clarify if WMH may serve as a general biomarker for cortical AD-associated pathology.