Work

Cholinergic Dysregulation in Alzheimer's Disease: A Meta‐Analysis of Enzymatic Activity and Regional Alterations in Brain and Cerebrospinal Fluid

Year: 2025

Type: article

Study designs: Systematic Review, Meta-Analysis

Abstract: Background Alzheimer's disease (AD), the leading cause of dementia, is characterized by β‐amyloid plaques, tau tangles, and early cholinergic dysfunction. This meta analysis examines changes in Butyrylcholinesterase (BChE), Acetylcholinesterase (AChE), Choline Acetyltransferase (ChAT), and choline levels in brain regions and cerebrospinal fluid (CSF) of AD patients versus healthy controls, highlighting their association with cognitive impairment. Method We searched MEDLINE, EMBASE, Cochrane, and Scopus for studies on BChE, AChE, ChAT activity, and choline levels in CSF and brain regions of AD patients, following PRISMA guidelines. Meta‐analysis used R's 'meta' package with inverse variance weighting to calculate mean concentrations and Standardized Mean Differences (SMDs). Heterogeneity was assessed using I 2 and T 2 , with T 2 estimated via restricted maximum‐likelihood and Q‐profile methods. Result AChE showed significant SMD of ‐1.00 (95% CI: ‐1.79 to ‐0.22, I 2 = 95.1%) in 22 studies (AD 414, 434 controls) in CSF. For brain regions, AChE showed significant SMD of ‐1.20 (95% CI: ‐1.58 to ‐0.83, I 2 = 63.9%) in 6 studies (AD 253, 180 controls), with the most significant SMDs of ‐1.70 (temporal), ‐1.87 (frontal), ‐1.48 (parietal), and ‐1.27 (hippocampal). BChE showed significant SMD of ‐0.55 (95% CI: ‐1.04 to ‐0.06, I 2 = 70.5%) in 8 studies (AD 159, 157 controls) in CSF. ChAT showed significant SMD of ‐2.21 (95% CI: ‐2.80 to ‐1.63, I 2 = 90.1%) in 13 studies (AD 471, 434 controls), with the most significant SMDs of ‐3.24 (frontal), ‐2.55 (hippocampal), ‐2.28 (temporal), and ‐1.81 (occipital). Choline showed a significant SMD of ‐0.87 (95% CI: ‐1.52 to ‐0.23, I 2 = 91.8%) in 5 studies (AD 311, 298 controls). Conclusion AChE showed significantly reduced activity in CSF and particularly in the temporal, frontal, hippocampal, and parietal brain regions. BChE exhibited significant reduction in CSF activity, and choline levels were significantly decreased in brain regions. ChAT showed significant reduction in the frontal, temporal, hippocampal, and occipital brain regions. Further research is required to validate these findings.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz70856_100992