Tangles and Plaques: A deep dive into the pathological hallmarks of Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. In AD, there is a gradual impairment of memory and cognitive function that interferes with daily living. The pathophysiology of AD revolves around complex interactions between amyloid-β (Aβ) overproduction and accumulation, followed by tau hyperphosphorylation, which together promote a cascade of neuronal dysfunction and degeneration. AD has two forms, sporadic and familial, with genetic variants such as triggering receptor expressed on myeloid cells-2 (TREM2). Various other variants also lead to impaired amyloid clearance and altered immune responses. Along with these genetic factors, aging remains the primary risk factor, and environmental as well as lifestyle factors can act synergistically to accelerate disease onset and progression. Although significant advances have been made in the last five decades, there has been only limited progress in the treatment because of a poor understanding of the molecular basis of AD. This makes current treatments largely focus on symptomatic management. This narrative review provides an updated synthesis of Alzheimer's disease pathophysiology, focusing on Aβ and tau pathology, glial activation, neuroinflammatory cascades, disrupted neurogenesis, and blood-brain barrier dysfunction. A focus and deeper understanding can help to develop new strategies that might work beyond the present conventional treatment. Due to the increasing global prevalence of AD, it is important to continue research into these mechanisms for the development of more effective interventions and improved patient outcomes.