Amyloid Beta and Tau Aggregation: The Etiology and Potential Pharmaceutical Approaches for Alzheimer’s Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized primarily by the accumulation of amyloid-β (Aβ) peptide and hyperphosphorylated, cleaved forms of the microtubule-associated protein tau. The probability of developing AD increases with age, mainly because the burdens of Aβ and tau pathology grow over time. Aβ plaques are composed of amyloid-β generated when β- and γ-secretases cleave the amyloid precursor protein (APP); these extracellular deposits disrupt neuronal homeostasis and ultimately trigger cell death. Neurofibrillary tangles formed by hyperphosphorylated tau compromise neuronal architecture and impair intracellular transport. This article discusses the formation of Aβ plaques and tau tangles as well as their potential modulation or clearance through interventions targeting molecules such as glycogen synthase kinase-3 (GSK-3) and fragment crystallizable receptors (FcRs). We also review the structures, mechanisms of action, neuropathological consequences, and synergistic effects of Aβ accumulation and tau phosphorylation. Monoclonal antibodies, including aducanumab and lecanemab, can slow plaque formation, neutralize Aβ toxicity, stimulate immune-mediated clearance, and remove existing aggregates. Tau-directed antibodies such as semorinemab and tilavonemab are currently in clinical trials and aim to lessen tau aggregation, stabilize microtubules, and inhibit pathogenic kinase activity. Advanced drug-delivery systems (e.g., exosome-loaded or peptide-conjugated nanoparticles) may facilitate the development of more precise, safer, and more potent therapeutics for AD.