Scholz Sonja W, Cobos Inma
Continuum (Minneap Minn). 2024 Dec 1;30(6):1801-1822. doi: 10.1212/CON.0000000000001505.
This article provides an overview of the current understanding of the genetic and pathologic features of neurodegenerative dementias, with an emphasis on Alzheimer disease and related dementias.
In recent years, there has been substantial progress in genetic research, contributing significant knowledge to our understanding of the molecular risk factors involved in neurodegenerative dementia syndromes. Several genes have been linked to monogenic forms of dementia (eg, APP, PSEN1, PSEN2, SNCA, GRN, C9orf72, MAPT) and an even larger number of genetic variants are known to influence susceptibility for developing dementia. As anti-amyloid therapies for patients with early-stage Alzheimer disease have entered the clinical arena, screening for the apolipoprotein E ε4 high-risk allele has come into focus, emphasizing the importance of genetic counseling. Similarly, advances in the pathologic classifications of neurodegenerative dementia syndromes and molecular pathology highlight their heterogeneity and overlapping features and provide insights into the pathogenesis of these conditions.
Recent progress in neurogenetics and molecular pathology has improved our understanding of the complex pathogenetic changes associated with neurodegenerative dementias, facilitating improved disease modeling, enhanced diagnostics, and individualized counseling. The hope is that this knowledge will ultimately pave the way for the development of novel therapeutics.
本文概述了目前对神经退行性痴呆的遗传和病理特征的认识，重点关注阿尔茨海默病及相关痴呆。
近年来，基因研究取得了重大进展，为我们理解神经退行性痴呆综合征所涉及的分子风险因素提供了重要知识。多个基因已与单基因形式的痴呆相关联（如APP、PSEN1、PSEN2、SNCA、GRN、C9orf72、MAPT），并且已知更多的基因变异会影响患痴呆的易感性。随着针对早期阿尔茨海默病患者的抗淀粉样蛋白疗法进入临床领域，对载脂蛋白E ε4高风险等位基因的筛查成为焦点，凸显了遗传咨询的重要性。同样，神经退行性痴呆综合征的病理分类和分子病理学的进展突出了它们的异质性和重叠特征，并为这些疾病的发病机制提供了见解。
神经遗传学和分子病理学的最新进展提高了我们对与神经退行性痴呆相关的复杂致病变化的理解，有助于改进疾病模型、加强诊断和提供个性化咨询。希望这些知识最终能为新型治疗方法的开发铺平道路。
