Toulouse Neuroimaging Center, Toulouse, France.
Toulouse Neuroimaging Center, Toulouse, France; Department of Cognitive Neurology, Epilepsy and Movement Disorders, CHU Toulouse Purpan, France.
Rev Neurol (Paris). 2023 Oct;179(8):812-830. doi: 10.1016/j.neurol.2022.12.006. Epub 2023 Mar 9.
Alzheimer's disease (AD) is a multi-etiology disease. The biological system of AD is associated with multidomain genetic, molecular, cellular, and network brain dysfunctions, interacting with central and peripheral immunity. These dysfunctions have been primarily conceptualized according to the assumption that amyloid deposition in the brain, whether from a stochastic or a genetic accident, is the upstream pathological change. However, the arborescence of AD pathological changes suggests that a single amyloid pathway might be too restrictive or inconsistent with a cascading effect. In this review, we discuss the recent human studies of late-onset AD pathophysiology in an attempt to establish a general updated view focusing on the early stages. Several factors highlight heterogenous multi-cellular pathological changes in AD, which seem to work in a self-amplifying manner with amyloid and tau pathologies. Neuroinflammation has an increasing importance as a major pathological driver, and perhaps as a convergent biological basis of aging, genetic, lifestyle and environmental risk factors.
阿尔茨海默病（AD）是一种多病因疾病。AD 的生物学系统与多领域遗传、分子、细胞和网络大脑功能障碍相关，与中枢和外周免疫相互作用。这些功能障碍主要是根据这样一种假设来概念化的，即大脑中的淀粉样蛋白沉积，无论是随机发生还是遗传意外，都是上游的病理变化。然而，AD 病理变化的分支表明，单一的淀粉样蛋白途径可能过于局限，或者与级联效应不一致。在这篇综述中，我们讨论了最近关于迟发性 AD 病理生理学的人类研究，试图建立一个关注早期阶段的普遍更新的观点。有几个因素突出了 AD 中异质的多细胞病理变化，这些变化似乎以淀粉样蛋白和 tau 病理为基础，以自我放大的方式发挥作用。神经炎症作为主要的病理驱动因素的重要性日益增加，也许是衰老、遗传、生活方式和环境风险因素的一个集中的生物学基础。
