Work

Biochemical mechanisms of acetylcholinesterase in Alzheimer’s disease pathogenesis and future therapeutic strategies

Year: 2026
Type: article
Abstract: Alzheimer’s disease is a major neurodegenerative disorder in which beta-amyloid (Aβ) proteins, tau pathology, neuroinflammation, and dysfunction of the cholinergic system interact to cause cognitive decline. Although acetylcholinesterase (AChE) has traditionally been viewed as the enzyme responsible for terminating cholinergic signals, growing evidence suggests that it also has non-catalytic interactions with beta-amyloid and tau proteins. It may affect amyloid-related pathways. However, the relative role and mechanistic significance of these non-traditional functions remain incompletely defined. This review summarizes the enzymatic, structural, and signaling roles of acetylcholinesterase in Alzheimer’s disease and examines the evidence linking this enzyme to beta-amyloid protein accumulation, tau pathology, and presenilin-1-associated amyloid processing. We also discuss cholinesterase inhibitors and emerging multi-target strategies, highlighting the distinction between symptom-related cholinergic improvement and potential disease-modifying effects. Overall, the enzyme acetylcholinesterase represents a therapeutically significant target, and its non-stimulatory functions warrant further investigation in experimental and clinical studies.
Language: English
Field: Medicine
Open Access status: diamond
OpenAlex ID: W7225199402
FWCI:
Cites: 151
Cited by:
Related to: 10