阿尔茨海默病Aβ免疫治疗的机制OA

Alzheimer's disease(AD)is a neurodegenerative disease characterized primarily by two core pathological features:abnormal deposition of β-amyloid(Aβ)around neurons in the cerebral cortex and hippocampus,and hyperphosphorylation of Tau protein.Based on the understanding that Aβ is derived from the pathological cleavage of amyloid precursor protein(APP)—and that Aβ exerts its pathogenic effects by damaging mitochondria,impairing synapses,and triggering neuroinflammation-this article notes that existing pharmacotherapies only alleviate symptoms.In contrast,Aβ immunotherapy has emerged as a key disease-modifying therapeutic strategy for AD,and immunotherapies targeting Aβ have become an important direction in AD disease-modifying therapy(DMT).This article systematically reviews the core mechanisms of Aβ immunotherapy,including the multi-dimensional roles of the immune system(such as Aβ clearance,inflammation regulation,and neuroprotection),as well as the characteristics of two major types of immunotherapies:passive immunotherapy with exogenous anti-Aβ monoclonal antibodies(such as Lecanemab and Donanemab),which take effect by activating phagocytosis and destroying plaques;and active immunotherapy,which induces antibodies through Aβ vaccines.New-generation vaccines optimize epitopes and adjuvants and have preventive potential.Additionally,the article provides an outlook on the clinical progress and future challenges of AD.