The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA.
Curr Neurol Neurosci Rep. 2021 Jan 19;21(2):4. doi: 10.1007/s11910-020-01090-y.
Early-onset Alzheimer's disease (EOAD), defined as Alzheimer's disease (AD) occurring before age 65, is significantly less well studied than the late-onset form (LOAD) despite EOAD often presenting with a more aggressive disease progression. The aim of this review is to summarize the current understanding of the etiology of EOAD, their translation into clinical practice, and to suggest steps to be taken to move our understanding forward.
EOAD cases make up 5-10% of AD cases but only 10-15% of these cases show known mutations in the APP, PSEN1, and PSEN2, which are linked to EOAD. New data suggests that these unexplained cases following a non-Mendelian pattern of inheritance is potentially caused by a mix of common and newly discovered rare variants. However, only a fraction of this genetic variation has been identified to date leaving the molecular mechanisms underlying this type of AD and their association with clinical, biomarker, and neuropathological changes unclear. While great advancements have been made in characterizing EOAD, much work is needed to disentangle the molecular mechanisms underlying this type of AD and to identify putative targets for more precise disease screening, diagnosis, prevention, and treatment.
早发性阿尔茨海默病（EOAD）定义为 65 岁以前发生的阿尔茨海默病（AD），尽管 EOAD 常表现出更具侵袭性的疾病进展，但与晚发性 AD（LOAD）相比，其研究明显较少。本文综述的目的是总结 EOAD 的病因学目前的认识，将其转化为临床实践，并提出推动我们的理解向前发展的步骤。
EOAD 病例占 AD 病例的 5-10%，但这些病例中只有 10-15%显示出与 EOAD 相关的 APP、PSEN1 和 PSEN2 中的已知突变。新数据表明，这些遵循非孟德尔遗传模式的未解释病例可能是由常见和新发现的罕见变异混合引起的。然而，迄今为止，只有一小部分遗传变异被识别出来，这使得 AD 的分子机制及其与临床、生物标志物和神经病理学变化的关联仍不清楚。虽然在描述 EOAD 方面已经取得了很大的进展，但仍需要做大量的工作来阐明这种 AD 的分子机制，并确定用于更精确的疾病筛查、诊断、预防和治疗的潜在靶点。
