Unravelling Alzheimer’s disease: Insights into pathophysiology, etiology, diagnostic approaches, and the promise of aducanumab, lecanemab, and donanemab

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that profoundly affects cognitive function, leading to memory loss and behavioural changes, and it stands as the leading cause of dementia worldwide.The pathophysiology of AD involves the buildup of amyloid-beta (Aß) plaques and neurofibrillary tangles formed by hyperphosphorylated tau protein, which contributes to neuronal dysfunction, synaptic loss, and brain atrophy.These pathological changes disrupt neuronal communication, resulting in the cognitive deficits observed in affected individuals.The etiology of AD is complex, influenced by genetic factors such as mutations in the amyloid precursor protein (APP) and presenilin genes, with the apolipoprotein E (APOE-e4) allele being a significant risk factor for late-onset AD.Additional factors include aging, oxidative stress, and vascular health.Diagnosis usually involves clinical assessments, neuropsychological testing, and neuroimaging methods like MRI and PET, along with biomarker evaluations in cerebrospinal fluid (CSF) and blood.While current treatments primarily target symptoms through cholinesterase inhibitors and NMDA receptor antagonists, recent advancements in disease-modifying therapies such as aducanumab, lecanemab, and donanemab represent a significant shift in treatment strategies.Aducanumab, approved by the FDA in 2021, was the first monoclonal antibody aimed at reducing amyloid plaques, although, its clinical benefits remain under discussion.Lecanemab and donanemab have demonstrated promise in slowing cognitive decline by targeting early amyloid deposition.This review explores the complex pathophysiology, etiology, and diagnostic methods of AD, highlighting the potential of these innovative therapies to change the disease trajectory and improve outcomes for patients.