Current Status and Developments in the Clinical Treatment of Alzheimers Disease

Alzheimers disease (AD) is a progressive neurodegenerative disorder which is characterized by extracellular amyloid-beta (A) plaque deposition, intracellular hyperphosphorylated tau neurofibrillary tangles (NFTs), synaptic dysfunction, and neuronal loss. Current therapeutic approaches, including acetylcholinesterase inhibitors and NMDA receptor antagonists, can only alleviate the symptoms but cannot prevent the progression of the disease. Emerging research on neurotrophic factors (NTFs) offers novel insights into disease-modifying therapies by targeting multiple pathological pathways. This comprehensive review elucidates the mechanistic roles of neurotrophic factors in AD, particularly focusing on the p75 neurotrophin receptor (p75NTR) and its downstream signaling cascades. Accumulating evidence highlights the pathological imbalance between pro-neurotrophins (proNGF/proBDNF) and mature neurotrophins, which exacerbates neuronal apoptosis via p75NTR-mediated pathways. Preclinical studies demonstrate that interventions targeting p75NTR, such as LM11A-31, a small-molecule ligand, effectively reduce A burden, tau hyperphosphorylation, and neuroinflammation. However, challenges including blood-brain barrier (BBB) penetration, long-term safety, and multi-target synergy remain unresolved. Future directions emphasize the development of advanced delivery systems, combinatorial therapies, and precision medicine strategies. This paper synthesizes current advancements in NTF-based therapies and proposes a roadmap for translational research in AD treatment.