Molecular and cellular mechanisms underlying Alzheimer’s disease: an integrated review

Abstract

Alzheimer’s disease (AD) is a multi-event neurodegenerative disease, typified by the development of cognitive deficits in conjunction with a range of genetic, molecular, cellular, and environmental processes. This review integrates evidence from more than 90 peer-reviewed publications across major domains of AD pathogenesis, including genetic risk factors (APOE, APP, and PSEN1/2); amyloid-β (Aβ) production, aggregation, and neurotoxicity; tau hyperphosphorylation and neurofibrillary tangle (NFT) formation; synaptic dysfunction; mitochondrial impairment and oxidative stress; neuroinflammation; and vascular dysfunction. Lifestyle and environmental modulators, such as sleep, nutrition, physical activity, and epigenetic influences, are also considered. By integrating these mechanisms, we provide a systems-level view in which interacting pathological pathways act in concert rather than independently to promote disease progression, and we discuss the therapeutic implications of this holistic model, including biomarker-based, multi-target precision approaches.

Keywords: Alzheimer disease, neurodegenerative disease, blood–brain barrier, pathological pathways, neuroinflammation, mitochondrial dysfunction, tau pathology, precision medicine