Alzheimer’s Disease: Molecular Mechanisms of the Disease and Involved Factors — A Comprehensive Narrative Review

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. Its hallmarks are extracellular amyloid-beta (Aβ) plaques and intracellular hyperphosphorylated tau forming neurofibrillary tangles, leading to synaptic dysfunction and neuronal loss. Despite extensive research, the mechanisms driving these proteinopathies and the contribution of genetic, molecular, and environmental factors remain unclear. Objective: This review summarizes the molecular mechanisms underlying AD and the factors influencing its onset and progression. Methods: A narrative review of peer-reviewed studies from PubMed, Scopus, and Web of Science was conducted. Relevant articles on neuropathology, molecular pathways, genetic susceptibility, oxidative stress, mitochondrial dysfunction, neuroinflammation, and metabolic and lifestyle risk factors were analyzed. Results: AD is marked by Aβ accumulation and tau pathology, causing synaptic and neuronal loss. Key mechanisms include abnormal amyloid precursor protein processing, tau hyperphosphorylation, oxidative stress, mitochondrial dysfunction, neuroinflammation, and calcium dysregulation. Genetic variants (APP, PSEN1, PSEN2, APOE ε4) increase risk, while aging, cardiovascular disease, diabetes, and lifestyle factors further influence disease onset and progression. Conclusion: AD arises from complex interactions among molecular and environmental factors. Understanding these pathways is essential for developing preventive strategies and effective therapies, with personalized approaches offering future promise.