Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) is the most common neuropathologic substrate of dementia. It is characterized by synapse loss (predominantly within neocortex) as well as deposition of certain distinctive lesions (the result of protein misfolding) throughout the brain. The latter include senile plaques, composed mainly of an amyloid (Aβ) core and a neuritic component; neurofibrillary tangles, composed predominantly of hyperphosphorylated tau; and cerebral amyloid angiopathy, a microangiopathy affecting both cerebral cortical capillaries and arterioles and resulting from Aβ deposition within their walls or (in the case of capillaries) immediately adjacent brain parenchyma. In this article, I discuss the hypothesized role these lesions play in causing cerebral dysfunction, as well as CSF and neuroimaging biomarkers (for dementia) that are especially relevant as immunotherapeutic approaches are being developed to remove Aβ from the brain parenchyma. In addition, I address the role of neuropathology in characterizing the sequelae of new AD/SDAT therapies and helping to validate CSF and neuroimaging biomarkers of disease. Comorbidity of AD/SDAT and various types of cerebrovascular disease is a major theme in dementia research, especially as cognitive impairment develops in the oldest old, who are especially vulnerable to ischemic and hemorrhagic brain lesions.

中文翻译：

---

阿尔茨海默氏病的新兴概念。

阿尔茨海默氏型痴呆/老年痴呆症（AD / SDAT）是痴呆症最常见的神经病理学基质。它的特征是突触丢失（主要在新皮层内），以及整个大脑中某些独特病变的沉积（蛋白质错误折叠的结果）。后者包括老年斑，主要由淀粉样蛋白（Aβ）核心和神经营养成分组成。神经原纤维缠结，主要由高磷酸化的tau组成；以及脑淀粉样血管病，一种微血管病，会影响大脑皮层毛细血管和小动脉，并且是由Aβ沉积在其壁内或（在毛细血管的情况下）紧邻脑实质的Aβ引起的。在本文中，我讨论了这些病变在引起脑功能障碍中的假设作用，随着正在开发从脑实质中去除Aβ的免疫治疗方法，CSF和神经影像生物标记物（用于痴呆症）尤其相关。此外，我将探讨神经病理学在表征新的AD / SDAT治疗后遗症中的作用，并帮助验证疾病的CSF和神经影像生物标志物。AD / SDAT和各种类型的脑血管疾病的合并症是痴呆症研究的主要主题，尤其是随着认知障碍在最老的老年人中发展而来，他们尤其容易遭受缺血性和出血性脑损伤。我将探讨神经病理学在表征新的AD / SDAT治疗后遗症中的作用，并帮助验证疾病的CSF和神经影像生物标记。AD / SDAT和各种类型的脑血管疾病的合并症是痴呆症研究的主要主题，尤其是随着认知障碍在最老的老年人中发展而来，他们尤其容易遭受缺血性和出血性脑损伤。我将探讨神经病理学在表征新的AD / SDAT治疗后遗症中的作用，并帮助验证疾病的CSF和神经影像生物标志物。AD / SDAT和各种类型的脑血管疾病的合并症是痴呆症研究的主要主题，尤其是随着认知障碍在最老的老年人中发展而来，他们尤其容易遭受缺血性和出血性脑损伤。