The selective vulnerability of specific neuronal subtypes is a hallmark of neurodegenerative diseases. In this Review, I summarize our current understanding of the brain regions and cell types that are selectively vulnerable in different neurodegenerative diseases and describe the proposed underlying cell-autonomous and non-cell-autonomous mechanisms. I highlight how recent methodological innovations — including single-cell transcriptomics, CRISPR-based screens and human cell-based models of disease — are enabling new breakthroughs in our understanding of selective vulnerability. An understanding of the molecular mechanisms that determine selective vulnerability and resilience would shed light on the key processes that drive neurodegeneration and point to potential therapeutic strategies to protect vulnerable cell populations.

特定神经元亚型的选择性脆弱性是神经退行性疾病的标志。在这篇综述中，我总结了我们目前对不同神经退行性疾病中选择性脆弱的大脑区域和细胞类型的理解，并描述了所提出的潜在细胞自主和非细胞自主机制。我强调最近的方法创新——包括单细胞转录组学、基于 CRISPR 的筛选和基于人类细胞的疾病模型——如何在我们对选择性脆弱性的理解上实现新的突破。了解决定选择性脆弱性和恢复力的分子机制将有助于揭示驱动神经变性的关键过程，并指出保护脆弱细胞群的潜在治疗策略。