Mechanisms Mediating the Protective Effects of Caffeine on Alzheimer’s Disease Progression

Background: This review aims to examine the molecular mechanisms through which caffeine may exert neuroprotective effects against Alzheimer’s Disease (AD). Methods: A literature review was done across PubMed and Embase to identify studies between 2000 and 2024, exploring the mechanism behind caffeine’s effects on AD. The criteria focused on peer-reviewed articles involving human or animal models. Information was gathered on study design, participant characteristics, caffeine consumption, proposed mechanisms, and effects on cognition. Results: The studies support caffeine's potential as a therapeutic, neuromodulator against AD through six mechanisms: inhibition of adenosine A2A receptors, decreased amyloid-beta production and aggregation, promotion of amyloid beta clearance, prevention of aberrant tau phosphorylation, induction of hippocampal neurogenesis, downregulation of AD-associated genes, and upregulation of an anti-inflammatory microglial phenotype. Discussion: We define six key neuroprotective mechanisms of caffeine against AD, which will allow us to understand the pathology of AD, and help us develop novel treatments. Future research on this topic should prioritize exploring these high-evidence mechanisms in human subjects studies.