Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
University of Milan, Dino Ferrari Centre, Milan, Italy.
J Alzheimers Dis. 2020;78(1):13-22. doi: 10.3233/JAD-200868.
Just as multiple sclerosis (MS) has long been primarily considered a white matter (WM) disease, Alzheimer's disease (AD) has for decades been regarded only as a grey matter disorder. However, convergent evidences have suggested that WM abnormalities are also important components of AD, at the same extent as axonal and neuronal loss is critically involved in MS pathophysiology since early clinical stages. These observations have motivated a more thorough investigation about the possible mechanisms that could link neuroinflammation and neurodegeneration, focusing on amyloid-β (Aβ). Neuroimaging studies have found that patients with AD have widespread WM abnormalities already at the earliest disease stages and prior to the presence of Aβ plaques. Moreover, a correlation between cerebrospinal fluid (CSF) Aβ levels and WM lesion load was found. On the other hand, recent studies suggest a predictive role for CSF Aβ levels in MS, possibly due in the first instance to the reduced capacity for remyelination, consequently to a higher risk of WM damage progression, and ultimately to neuronal loss. We undertook a review of the recent findings concerning the involvement of CSF Aβ levels in the MS disease course and of the latest evidence of AD related WM abnormalities, with the aim to discuss the potential causes that may connect WM damage and amyloid pathology.
正如多发性硬化症（MS）长期以来主要被认为是一种白质（WM）疾病，阿尔茨海默病（AD）几十年来也仅被视为一种灰质疾病。然而，越来越多的证据表明，WM 异常也是 AD 的重要组成部分，与 MS 病理生理学中的轴突和神经元丢失一样，在早期临床阶段就至关重要。这些观察结果促使人们更深入地研究可能将神经炎症和神经退行性变联系起来的机制，重点关注淀粉样蛋白-β（Aβ）。神经影像学研究发现，AD 患者在疾病的最早阶段，即在 Aβ斑块出现之前，就已经存在广泛的 WM 异常。此外，还发现脑脊液（CSF）Aβ水平与 WM 病变负荷之间存在相关性。另一方面，最近的研究表明 CSF Aβ水平在 MS 中的预测作用，可能首先是由于少突胶质细胞再生能力降低，因此 WM 损伤进展的风险更高，最终导致神经元丢失。我们回顾了最近关于 CSF Aβ水平在 MS 病程中的作用的发现，以及与 AD 相关的 WM 异常的最新证据，旨在讨论可能将 WM 损伤和淀粉样蛋白病理学联系起来的潜在原因。
