The Alzheimer's disease (AD) afflicted brain is neuropathologically defined by extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated tau protein. However, accumulating evidence suggests that the presynaptic protein α-synuclein (αSyn), mainly associated with synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), is involved in the pathophysiology of AD. Lewy-related pathology (LRP), primarily comprised of αSyn, is present in a majority of autopsied AD brains, and higher levels of αSyn in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) and AD have been linked to cognitive decline. Recent studies also suggest that the asymptomatic accumulation of Aβ plaques is associated with higher CSF αSyn levels in subjects at risk of sporadic AD and in individuals carrying autosomal dominant AD mutations. Experimental evidence has further linked αSyn mainly to tau hyperphosphorylation, but also to the pathological actions of Aβ and the APOEε4 allele, the latter being a major genetic risk factor for both AD and DLB. In this review, we provide a summary of the current evidence proposing an involvement of αSyn either as an active or passive player in the pathophysiological ensemble of AD, and furthermore describe in detail the current knowledge of αSyn structure and inferred function.

中文翻译：

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α-突触核蛋白在阿尔茨海默氏病的病理生理中。

患阿尔茨海默氏病（AD）的神经病理学定义为细胞外淀粉样β（Aβ）斑块和由高磷酸化tau蛋白组成的神经内神经原纤维缠结。然而，越来越多的证据表明，突触前蛋白α-突触核蛋白（αSyn）主要与突触核病如帕金森氏病（PD），路易体痴呆（DLB）和多系统萎缩（MSA）有关，与AD的病理生理有关。大部分尸检的AD脑中都存在主要由αSyn组成的路易相关病理学（LRP），与轻度认知障碍（MCI）和AD的患者的脑脊液（CSF）中较高水平的αSyn相关联认知能力下降。最近的研究还表明，在有散发性AD风险的受试者和携带常染色体显性AD突变的个体中，Aβ斑块的无症状积累与较高的CSFαSyn水平相关。实验证据进一步证实αSyn主要与tau过度磷酸化有关，但也与Aβ和APOEε4等位基因的病理作用有关，后者是AD和DLB的主要遗传危险因素。在这篇综述中，我们提供了目前证据的概述，提出了αSyn作为AD病理生理学中的主动或被动参与者的参与，并且进一步详细描述了αSyn结构和推断功能的当前知识。实验证据进一步证实αSyn主要与tau过度磷酸化有关，但也与Aβ和APOEε4等位基因的病理作用有关，后者是AD和DLB的主要遗传危险因素。在这篇综述中，我们提供了目前证据的概述，提出了αSyn作为AD病理生理学中的主动或被动参与者的参与，并且进一步详细描述了αSyn结构和推断功能的当前知识。实验证据进一步证实αSyn主要与tau过度磷酸化有关，但也与Aβ和APOEε4等位基因的病理作用有关，后者是AD和DLB的主要遗传危险因素。在这篇综述中，我们提供了目前证据的概述，提出了αSyn作为AD病理生理学中的主动或被动参与者的参与，并且进一步详细描述了αSyn结构和推断功能的当前知识。