Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Alzheimer's Disease: Recent Advances and Controversies.

Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by the gradual deterioration of memory, imposes a significant global socioeconomic burden. Despite mechanistic insights into amyloid-β (Aβ) and tau pathways, effective therapies remain elusive. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism, has emerged as a multifunctional player in neurodegenerative processes. Initially studied for its role in cardiovascular health, recent evidence implicates PCSK9 in AD pathogenesis through mechanisms involving Aβ clearance, neuroinflammation, and receptor-mediated cholesterol trafficking. However, conflicting genetic and clinical data complicate its therapeutic potential. This review synthesizes current knowledge on PCSK9's role in AD, highlighting molecular pathways, clinical controversies, and implications for therapeutic development. Resolving these complexities could advance targeted diagnostics and disease-modifying therapies.