Alzheimer's Disease: A Comprehensive Review of Pathogenesis, Diagnostic Biomarkers, Clinical Progression, and Evolving Therapeutics

Alzheimer's disease (AD) is the major cause of dementia worldwide and a progressive neurodegenerative disorder, accounting for 60–70% of the estimated 55 million global cases of dementia. The core neuropathological hallmarks, extracellular amyloid-beta (Aβ) plaques and intraneuronal neurofibrillary tangles (NFTs) of hyperphosphorylated tau, activate a complex pathophysiological cascade including chronic neuroinflammation, reactive microgliosis, astrocytic dysfunction, mitochondrial failure, oxidative stress, synaptic breakdown and extensive neuronal loss. The historical reliance on late-stage syndromic definitions has now been replaced by a rigorous biological framework (Revised 2024 Criteria and AT (N) staging), enabling disease identification years prior to overt dementia via cerebrospinal fluid (CSF) assays, molecular positron emission tomography (PET), and increasingly studied blood-based biomarkers such as plasma phosphorylated-tau217 (p-tau217). Conventional pharmacotherapies (acetylcholinesterase inhibitors and memantine) provide modest symptomatic stabilization without altering disease pathology. In contrast, recently approved disease-modifying monoclonal antibodies (lecanemab and donanemab) clear cerebral amyloid plaques and modestly slow cognitive and functional decline in early symptomatic stages. But these therapies have clinical challenges including amyloid-related imaging abnormalities (ARIA), high cost and infrastructure needs. At the same time, multi-domain non-pharmacological approaches, such as structured physical exercise, cognitive stimulation, nutritional optimization and caregiver support, continue to be fundamental pillars of holistic care. This review summarizes the current evidence for the epidemiology of AD, its multifactorial etiology, molecular pathophysiology, clinical course, biological diagnostic criteria, evidence-based pharmacotherapies and emerging precision therapeutics.