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The Role of Amyloid-β in White Matter Damage: Possible Common Pathogenetic Mechanisms in Neurodegenerative and Demyelinating Diseases.
Journal of Alzheimer’s Disease ( IF 3.4 ) Pub Date : 2020-09-08 , DOI: 10.3233/jad-200868
Anna M Pietroboni 1, 2 , Annalisa Colombi 2 , Tiziana Carandini 1, 2 , Elio Scarpini 1, 2 , Daniela Galimberti 1, 2 , Marco Bozzali 3, 4
Affiliation  

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 sameextent 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.

中文翻译:

淀粉样蛋白-β 在白质损伤中的作用:神经退行性疾病和脱髓鞘疾病中可能的常见发病机制。

正如多发性硬化症 (MS) 长期以来主要被认为是一种白质 (WM) 疾病一样,阿尔茨海默病 (AD) 几十年来也仅被视为一种灰质疾病。然而,综合证据表明 WM 异常也是 AD 的重要组成部分,与轴突和神经元丢失在临床早期阶段就与 MS 病理生理学密切相关的程度相同。这些观察结果促使对可能将神经炎症和神经变性联系起来的可能机制进行更彻底的调查,重点是淀粉样蛋白-β (Aβ)。神经影像学研究发现,AD 患者在疾病的最早阶段和 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,脑脊液 Aβ 水平在 MS 中具有预测作用,这可能首先是由于髓鞘再生能力降低,从而导致 WM 损伤进展的风险更高,并最终导致神经元丢失。我们回顾了最近关于 CSF Aβ 水平参与 MS 病程的发现以及 AD 相关 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联系起来的潜在原因。
更新日期:2020-09-08
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