Background: Alzheimer's disease (AD) is a complex disorder involving neuroinflammation, vascular impairment, and synaptic dysfunction. This meta‐analysis aims to evaluate and compare dopamine, serotonin, and norepinephrine levels across brain regions in AD patients and healthy controls, exploring their potential as early diagnostic biomarkers. Method: We searched MEDLINE, EMBASE, Cochrane, and Scopus for studies on dopamine, serotonin, and norepinephrine concentrations in AD patients, following PRISMA guidelines. The meta‐analysis utilized R's 'meta' package to calculate standardized mean differences (SMD) and assess heterogeneity using I ² and tau ² . Result: Our comprehensive analysis of multiple brain tissues revealed significant alterations in specific brain regions of AD patients compared to healthy controls. Serotonin exhibited a substantial SMD of ‐1.92 (95% CI: ‐2.43 to ‐1.40, I ² = 78.1%) across 9 studies (242 AD, 241 controls), with the greatest reduction in the hippocampal region (SMD: ‐2.53, 95% CI: ‐3.77 to ‐1.29), followed by the thalamus (SMD: ‐2.19, 95% CI: ‐3.00 to ‐1.39), temporal region (SMD: ‐1.87, 95% CI: ‐2.72 to ‐1.02), and frontal region (SMD: ‐1.52, 95% CI: ‐2.08 to ‐0.96). Dopamine showed a significant overall SMD of ‐0.55 (95% CI: ‐0.93 to ‐0.17, I ² = 55.5%) across 5 studies (154 AD, 133 controls), with the most pronounced reductions in the frontal (SMD: ‐0.82, 95% CI: ‐1.38 to ‐0.27) and temporal regions (SMD: ‐0.71, 95% CI: ‐1.37 to ‐0.06). Norepinephrine exhibited a notable SMD of ‐1.84 (95% CI: ‐2.52 to ‐1.15, I ² = 83.1%) in 5 studies (197 AD, 183 controls), with the greatest reductions in the hippocampal region (SMD: ‐2.70, 95% CI: ‐4.18 to ‐1.22), frontal region (SMD: ‐2.17, 95% CI: ‐3.92 to ‐0.43), and thalamus (SMD: ‐2.12, 95% CI: ‐3.05 to ‐1.19). Conclusion: Serotonin, dopamine, and norepinephrine levels were significantly reduced in specific brain regions in AD. The most substantial decrease in serotonin was observed in the hippocampus, thalamus, temporal, and frontal regions. Dopamine levels were notably reduced in the temporal and frontal regions, while norepinephrine showed significant reductions in the hippocampus, thalamus, and frontal regions. Further validation of these findings is required.

Background: Neuropeptides are crucial proteins in the central nervous system, which significantly influence neurophysiological processes. This analysis explores cerebrospinal fluid alterations in Alzheimer's disease, offering insights to better understand the condition and explore novel diagnostic and therapeutic avenues.Method: We systematically searched MEDLINE (PubMed), EMBASE, Cochrane, and Scopus using specific search strategies. Following PRISMA guidelines, our screening and extraction included studies that investigated neuropeptide concentrations in Alzheimer's patients' cerebrospinal fluid (CSF). Utilizing the 'meta' R package, particularly the 'metacont' tool, we analyzed mean concentration levels and standard differences via the random effects model. Data pooling utilized inverse variance weighting, with I² and tau² assessing heterogeneity. The restricted maximum−likelihood estimator and Q−profile informed tau² and its confidence interval. The primary outcome was the mean difference in CSF neuropeptide levels between Alzheimer's patients and controls, considering reported units separately.Result: In our analysis of neuropeptides across diverse studies involving Alzheimer's Disease (AD) patients and controls, we observed distinct neurochemical alterations. Somatostatin showed a significant mean difference of ‐15.48 pg/mL (95% CI: ‐20.95 to ‐10.01, I² = 89%) in 9 studies (141 AD, 203 controls), and ‐8.05 pmol/L difference (95% CI: ‐13.35 to ‐2.76, I² = 0%) in 2 studies (44 AD, 57 controls). Neuropeptide Y (NPY) showed ‐8.83 pg/mL difference (95% CI: ‐19.81 to 2.16, I² = 65%) in 5 studies (76 AD, 95 controls), and ‐16.85 pmol/L difference (95% CI: ‐35.21 to 1.52, I² = 71%) in 3 studies (87 AD, 62 controls). Orexin exhibited a difference of 8.03 pg/mL (8 studies: 235 AD, 177 controls; ‐2.60; 18.67, I² = 27%, p‐value: 0.14). After excluding a study that significantly reduced heterogeneity, the adjusted result was 12.77 (95% CI: 1.16 ‐ 24.39, p‐value: 0.03). Substance P also showed a reduction in mean difference by ‐16.52 pg/mL (2 studies: 45 AD, 35 controls; ‐67.47; 34.42, I² = 87%) but was not statistically significant.Conclusion: Somatostatin exhibited a consistent decrease in levels across studies, indicating potential relevance to AD pathophysiology. Additionally, orexin demonstrated a significant increase in levels in individuals diagnosed with Alzheimer's.

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.