20.500.12556/RUL-187854 Genetic and functional dynamics of butyrylcholinesterase in Alzheimer's disease from mechanisms to clinical relevance Butyrylcholinesterase (BChE), once regarded as a redundant cholinesterase, has emerged as an important modulator of Alzheimer's disease (AD). Unlike acetylcholinesterase (AChE), which declines during disease progression, BChE activity is preserved or elevated in the AD brain and becomes the predominant cholinesterase in advanced stages. Beyond its enzymatic role in acetylcholine hydrolysis, BChE is directly associated with amyloid plaques and tau pathology and has been implicated in neuroinflammatory processes. Genetic variants of the BCHE gene, most notably the K-variant, further contribute to inter-individual differences in AD susceptibility, disease onset, and therapeutic response, particularly in the context of APOE4. Evidence from biochemical, histological, and clinical studies indicates that BChE influences both the pathophysiology of AD and the effectiveness of cholinesterase inhibitor therapy, with rivastigmine providing unique benefits through dual AChE and BChE inhibition. Recent efforts to develop selective or multitarget BChE inhibitors underscore the enzyme's potential as a therapeutic target, while BChE-specific positron emission tomography tracers highlight its diagnostic promise by distinguishing AD-related amyloid plaques from those of normal aging. Despite these advances, uncertainties remain regarding the precise dynamics of BChE activity across disease stages, its contribution to plaque maturation and inflammation, and its influence on responses to novel anti-amyloid antibody therapies. Overall, BChE represents a multifaceted factor in AD pathogenesis, therapy, and biomarker development, warranting further genotype-stratified and mechanistic investigations to clarify its clinical utility. Alzheimer's disease butyrylcholinesterase cholinesterase inhibitors genetic variants Alzheimerjeva bolezen butirilholinesteraza zaviralci holinesteraze genetske variante true false true Angleški jezik Slovenski jezik Članek v reviji 2026-09-15 11:33:46 2026-09-15 11:33:54 2026-09-17 04:29:39 0000-00-00 00:00:00 2026 0 0 10 str. art. 111809 Vol. 423 2026 0000-00-00 PostprintKoncna Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.2 1872-7786 10.1016/j.cbi.2025.111809 267470851 RAZ_Presern_Uros_2026.pdf RAZ_Presern_Uros_2026.pdf 1 F751D916364E13A821C58F26968DF6CC bca63a34ee32776d92c0bf9142dca10a5306fed911ab7103df43a15e17de7136 11b398d6-b193-11f1-8bc5-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=247718 https://www.sciencedirect.com/science/article/abs/pii/S0009279725004399 0 8a93bf99-b0e8-11f1-8bc5-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=247657 Medicinska fakulteta 0 0 0