Mehta Rashi I, Mehta Rupal I
Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA.
Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA.
Biomedicines. 2023 Jan 30;11(2):408. doi: 10.3390/biomedicines11020408.
Alzheimer's disease (AD) is a devastating and irreversible neurodegenerative disorder with unknown etiology. While its cause is unclear, a number of theories have been proposed to explain the pathogenesis of AD. In large part, these have centered around potential causes for intracerebral accumulation of beta-amyloid (βA) and tau aggregates. Yet, persons with AD dementia often exhibit autopsy evidence of mixed brain pathologies including a myriad of vascular changes, vascular brain injuries, complex brain inflammation, and mixed protein inclusions in addition to hallmark neuropathologic lesions of AD, namely insoluble βA plaques and neurofibrillary tangles (NFTs). Epidemiological data demonstrate that overlapping lesions diminish the βA plaque and NFT threshold necessary to precipitate clinical dementia. Moreover, a subset of persons who exhibit AD pathology remain resilient to disease while other persons with clinically-defined AD dementia do not exhibit AD-defining neuropathologic lesions. It is increasingly recognized that AD is a pathologically heterogeneous and biologically multifactorial disease with uncharacterized biologic phenomena involved in its genesis and progression. Here, we review the literature with regard to neuropathologic criteria and incipient AD changes, and discuss converging concepts regarding vascular and immune factors in AD.
阿尔茨海默病（AD）是一种病因不明的毁灭性且不可逆的神经退行性疾病。尽管其病因尚不清楚，但已提出了一些理论来解释AD的发病机制。在很大程度上，这些理论都围绕着β-淀粉样蛋白（βA）和tau蛋白聚集体在脑内积累的潜在原因。然而，患有AD痴呆症的人尸检时往往显示出混合性脑病理证据，除了AD的标志性神经病理病变，即不溶性βA斑块和神经原纤维缠结（NFTs）外，还包括大量血管变化、血管性脑损伤、复杂的脑炎症和混合性蛋白质包涵体。流行病学数据表明，重叠性病变会降低引发临床痴呆所需的βA斑块和NFT阈值。此外，一部分表现出AD病理特征的人对疾病具有抵抗力，而其他临床诊断为AD痴呆症的人却没有表现出AD特征性神经病理病变。人们越来越认识到，AD是一种病理异质性和生物学多因素疾病，其发生和发展涉及尚未明确的生物学现象。在此，我们回顾了有关神经病理学标准和早期AD变化的文献，并讨论了关于AD中血管和免疫因素的趋同概念。
