Progress in the diagnosis and treatment of Alzheimer's disease

Abstract

This review systematically describes the advances in the diagnosis and treatment of Alzheimer's disease (AD). The core pathological features of AD are β-amyloid protein (Aβ) deposition and neurofibrillary tangles formed by hyperphosphorylated tau protein. Its pathogenesis is complex, involving the Aβ hypothesis, the Tau hypothesis, the cholinergic hypothesis and, the inflammation hypothesis, and they are significantly affected by genetic factors (such as familial AD gene APP / PSEN 1 / PSEN 2 and sporadic AD risk gene APOE ε4). In terms of diagnosis, the development of cerebrospinal fluid biomarkers (e.g., t-tau, p-tau) and imaging techniques (amyloid PET, Tau PET, sMRI, FDG-PET) greatly improves the precision of early diagnosis, differential diagnosis, and disease progression monitoring. Current treatment mainly includes symptom improvement drugs: cholinesterase inhibitors (donepezil, etc.) to improve cholinergic function, NMDA receptor antagonists (memantine) to reduce excitotoxicity, often combined but unable to change the course of the disease. The breakthrough was the anti-Aβ monoclonal antibody (e.g., Lecanemab) as a disease-modifying therapy that proved to clear A β plaques in clinical trials and significantly reduce cognitive decline in early AD patients, despite challenges such as safety (e.g., ARIA), cost, and applicable population (early only). Future research aims to optimize existing therapies, develop new target drugs (e.g., anti-tau and anti-inflammatory), explore combination strategies, improve early diagnosis capabilities, and expand treatment accessibility to achieve the goal of effectively preventing and delaying the AD process.