Butovsky Oleg, Rosenzweig Neta
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Immunity. 2025 May 13;58(5):1120-1139. doi: 10.1016/j.immuni.2025.04.013. Epub 2025 May 4.
Alzheimer's disease (AD) and age-related macular degeneration (AMD) represent the leading causes of dementia and vision impairment in the elderly, respectively. The retina is an extension of the brain, yet these two central nervous system (CNS) compartments are often studied separately. Despite affecting cognition vs. vision, AD and AMD share neuroinflammatory pathways. By comparing these diseases, we can identify converging immune mechanisms and potential cross-applicable therapies. Here, we review immune mechanisms highlighting the shared and distinct aspects of these two age-related neurodegenerative conditions, focusing on responses to hallmark disease manifestations, the opposite role of overlapping immune risk loci, and potential unified therapeutic approaches. We also discuss unique tissue requirements that may dictate different outcomes of conserved immune mechanisms and how we can reciprocally utilize lessons from AD therapeutics to AMD. Looking forward, we suggest promising directions for research, including the exploration of regenerative medicine, gene therapies, and innovative diagnostics.
阿尔茨海默病（AD）和年龄相关性黄斑变性（AMD）分别是老年人痴呆和视力损害的主要原因。视网膜是大脑的延伸，但这两个中枢神经系统（CNS）部分通常是分开研究的。尽管AD和AMD分别影响认知和视力，但它们共享神经炎症途径。通过比较这些疾病，我们可以识别趋同的免疫机制和潜在的交叉适用疗法。在这里，我们回顾免疫机制，突出这两种与年龄相关的神经退行性疾病的共同和不同方面，重点关注对标志性疾病表现的反应、重叠免疫风险位点的相反作用以及潜在的统一治疗方法。我们还讨论了可能决定保守免疫机制不同结果的独特组织需求，以及我们如何相互借鉴AD治疗学对AMD的经验教训。展望未来，我们提出了有前景的研究方向，包括再生医学、基因疗法和创新诊断方法的探索。
