Caffeine as a modulator of neurodegenerative processes: molecular targets, dose-dependent effects, and the influence of genetic polymorphism

Neurodegenerative diseases represent one of the most significant and rapidly growing public health challenges globally. Since no effective treatments are available to stop or reverse their progression, the scientific community is paying closer attention to modifiable risk factors, including diet and lifestyle. In this context, caffeine, being the most widely consumed psychoactive substance in the world, is becoming the object of close study as a potential factor that can influence the abnormal neurodegeneration processes. Objective. To conduct a systematic analysis of the caffeine effect on the molecular mechanisms of neurodegeneration in Parkinson’s and Alzheimer’s diseases, assessing the role of genetic factors and dose-dependent effects in providing neuroprotective action. Materials and methods. Publications in the PubMed, Scopus, Web of Science, and Google Scholar databases were searched using the keywords «caffeine», «neurodegeneration», «Parkinson’s disease», «Alzheimer’s disease», and «neuroprotection». The papers were selected based on their methodological quality and relevance over the past few years. Results. Epidemiological evidence supports an inverse association between moderate caffeine intake and a reduced risk of Parkinson’s disease, which is likely due to adenosine receptor antagonism. For Alzheimer’s, the link is less clear, and some studies suggest that coffee’s neuroprotective effect may be due to other compounds, such as phenylindanes, rather than caffeine itself. Experimental evidence also indicates potential neurotoxic effects of caffeine associated with excessive doses, sleep disturbances, and specific conditions such as traumatic brain injury. Conclusion. Contradictions in studies highlight the critical role of individual genetic variation, particularly polymorphisms in the CYP1A2 and ADORA2A genes that determine caffeine metabolism and sensitivity. These findings suggest against universal recommendations for caffeine intake. Future research should consider genetic profiles to develop personalized neuroprophylaxis strategies.