Genetic, epigenetic, environmental, and technological determinants of neurodegenerative diseases: an integrative approach to Alzheimer's, Parkinson's, and Huntington's diseases and Amyotrophic Lateral Sclerosis

Neurodegenerative diseases represent a major challenge to neurological health because their development results from complex interactions among genetic susceptibility, epigenetic regulation, environmental exposures, aging, and cellular dysfunction. Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis illustrate distinct but partially convergent pathways involving neuroinflammation, mitochondrial dysfunction, impaired proteostasis, oxidative stress, and neuronal vulnerability. Beyond traditional biological determinants, technological and behavioral changes have introduced new dimensions to the study of brain health, including digital technologies, social media-related factors, artificial intelligence, and digital biomarkers. This review integrates these dimensions to examine how genome, epigenome, exposome, cellular environment, and technological influences may interact across multiple levels of neurodegenerative disease mechanisms. It further discusses how emerging technologies may contribute to earlier detection, risk characterization, prevention research, and more personalized approaches to neurological care.