CD36 is a membrane protein with wide distribution in the human body, is enriched in the monocyte-macrophage system and endothelial cells, and is involved in the cellular uptake of long chain fatty acids (LCFA) and oxidized low-density lipoproteins. It is also a scavenger receptor, binding hydrophobic amyloid fibrils found in the Alzheimer’s disease (AD) brain. In neurobiology research, it has been mostly studied in relationship with chronic ischemia and stroke, but it was also related to amyloid clearance by microglial phagocytosis. In AD animal models, amyloid binding to CD36 has been consistently correlated with a pro-inflammatory response. Therapeutic approaches have two main focuses: CD36 blockade with monoclonal antibodies or small molecules, which is beneficial in terms of the inflammatory milieu, and upregulation of CD36 for increased amyloid clearance. The balance of the two approaches, centered on microglia, is poorly understood. Furthermore, CD36 evaluation in AD clinical studies is still at a very early stage and there is a gap in the knowledge regarding the impact of LCFA on AD progression and CD36 expression and genetic phenotype. This review summarizes the role played by CD36 in the pathogenic amyloid cascade and explore the translatability of preclinical data towards clinical research.

CD36是一种在人体内广泛分布的膜蛋白，在单核-巨噬细胞系统和内皮细胞中富集，参与长链脂肪酸（LCFA）和氧化低密度脂蛋白的细胞摄取。它也是一种清道夫受体，结合在阿尔茨海默病 (AD) 大脑中发现的疏水性淀粉样蛋白原纤维。在神经生物学研究中，主要研究它与慢性缺血和中风的关系，但也与小胶质细胞吞噬作用的淀粉样蛋白清除有关。在 AD 动物模型中，与 CD36 结合的淀粉样蛋白一直与促炎反应相关。治疗方法有两个主要重点：用单克隆抗体或小分子阻断 CD36，这对炎症环境有益，和 CD36 的上调以增加淀粉样蛋白的清除。以小胶质细胞为中心的这两种方法的平衡，人们知之甚少。此外，AD 临床研究中的 CD36 评估仍处于非常早期的阶段，关于 LCFA 对 AD 进展和 CD36 表达和遗传表型的影响的知识存在差距。本综述总结了 CD36 在致病性淀粉样蛋白级联中所起的作用，并探讨了临床前数据对临床研究的可转化性。