Alzheimer's Disease Investigated via Gene-Environment Interactions, Biochemical Pathways, Cellular Processes, and Disease Phenotype Variability

Abstract

Background: Alzheimer's disease (AD) is a neurodegenerative disorder influenced by genetic and environmental factors. APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, and CD33 play key roles in AD pathogenesis, affecting biochemical pathways and cellular processes. However, the interaction between genetic predisposition and environmental factors, as well as the reasons for variability in disease phenotype, remain poorly understood. This study aims to investigate these interactions to improve our understanding of AD etiology and inform personalized interventions. Methods: A comprehensive search encompassing databases such as PubMed, MEDLINE, Google Scholar, and open access/subscription-based journals was conducted to retrieve relevant articles for the investigation of genes involved in Alzheimer's disease (AD) pathogenesis, including APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, and CD33. Articles were searched without any date restrictions. Utilizing the criteria delineated in the methodology section, studies were systematically reviewed to elucidate how environmental factors and genetics influence Alzheimer's disease onset, progression, symptom severity, and progression rates. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: Our investigation revealed the complicated interactions between genetic predisposition, environmental factors, biochemical pathways, and cellular processes in Alzheimer's disease (AD) pathogenesis. APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, and CD33 influence amyloid-beta production, tau pathology, lipid metabolism, and inflammation in AD. These genes interact with environmental factors such as diet, pollutants, head trauma, and lifestyle, modulating disease risk and progression. Additionally, we found variability in disease phenotype among individuals carrying similar genetic mutations, influenced by genetic modifiers, environmental factors, cognitive reserve, and neurobiological differences. Conclusion: Alzheimer's disease (AD) is a multifactorial disorder influenced by genetic and environmental factors. APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, and CD33 play critical roles in AD pathogenesis by affecting amyloid-beta production, tau pathology, lipid metabolism, and inflammation. These genes interact with environmental factors such as diet, pollutants, head trauma, and lifestyle, further modulating disease risk and progression. Understanding these complicated interactions is essential for developing personalized interventions to delay onset, reduce severity, and slow AD progression.