Ramanan Vijay K, Graff-Radford Jonathan
Continuum (Minneap Minn). 2024 Dec 1;30(6):1726-1743. doi: 10.1212/CON.0000000000001499.
Although Alzheimer disease (AD) is the most common neurodegenerative cause of dementia, neurologists must be aware of other etiologies that can mimic the amnestic-predominant syndrome and medial temporal brain involvement typically associated with AD. This article reviews recent updates surrounding limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy (LATE), hippocampal sclerosis, and primary age-related tauopathy.
LATE neuropathologic change occurs in approximately 40% of autopsied older adults, including occurrences in isolation in some older individuals with amnestic cognitive impairment. LATE neuropathologic change is often, but not always, associated with hippocampal sclerosis (neuronal loss and gliosis in the hippocampus and associated structures) and frequently coexists with AD and other neurodegenerative pathologies. Although there is no direct clinical biomarker for TDP-43 pathology, recent studies suggest that a clinical diagnosis of LATE can be achieved through the integration of multiple data points. Primary age-related tauopathy refers to the pathologic finding (in some cognitively unimpaired older adults as well as some individuals with cognitive impairment) of medial temporal-predominant neurofibrillary tangles in the absence of amyloid-β (Aβ) plaques. Recent consensus frameworks have attempted to resolve ambiguities of nomenclature and diagnosis for these entities, and efforts toward in vivo biomarkers are ongoing.
LATE, with or without hippocampal sclerosis, and primary age-related tauopathy belong in the differential diagnosis (along with AD, argyrophilic grain disease, and other disorders) for slowly progressive amnestic-predominant cognitive impairment, particularly in individuals older than 75 years. Accurate recognition of clinical and diagnostic test features supportive of these non-AD entities is vital to optimize patient counseling, therapeutic selection, and novel biomarker development.
尽管阿尔茨海默病（AD）是痴呆最常见的神经退行性病因，但神经科医生必须了解其他可能模仿以遗忘为主综合征以及通常与AD相关的内侧颞叶脑受累的病因。本文综述了围绕边缘叶为主的年龄相关的反应性DNA结合蛋白43（TDP-43）脑病（LATE）、海马硬化和原发性年龄相关tau蛋白病的最新进展。
LATE神经病理改变发生在约40%的老年尸检病例中，包括一些有遗忘性认知障碍的老年个体中单独出现的情况。LATE神经病理改变常（但不总是）与海马硬化（海马及相关结构中的神经元丢失和胶质增生）相关，并经常与AD和其他神经退行性病变共存。尽管尚无针对TDP-43病理的直接临床生物标志物，但最近的研究表明，通过整合多个数据点可实现LATE的临床诊断。原发性年龄相关tau蛋白病是指在无淀粉样β（Aβ）斑块的情况下，以内侧颞叶为主的神经原纤维缠结的病理表现（在一些认知未受损的老年人以及一些有认知障碍的个体中）。最近的共识框架试图解决这些实体在命名和诊断方面的模糊性，并且针对体内生物标志物的研究正在进行中。
LATE，无论有无海马硬化，以及原发性年龄相关tau蛋白病都属于以缓慢进展的遗忘为主的认知障碍的鉴别诊断（与AD、嗜银颗粒病和其他疾病一起），特别是在75岁以上的个体中。准确识别支持这些非AD实体的临床和诊断测试特征对于优化患者咨询、治疗选择和新型生物标志物开发至关重要。
