Neuroinflammation plays a critical role in Alzheimer's (AD) and Parkinson's diseases (PD) onset, pathophysiology, and progression. The aim of our meta-analysis was to review the available literature to assess the role of neuroinflammation in the pathogenesis of the two most common neurological diseases: Parkinson's disease and Alzheimer's disease. Two medical databases were searched: Web of Science and PubMed in the period from 2009-2023, where a total of 37 publications that met the inclusion criteria were selected for further evaluation. Both patients with AD and with PD showed statistically significantly higher levels of interleukin IL-6 compared to the control group: p-value of 0.0034 for AD (SMD, 1.17; 95% CI, 0.39-1.96) and p-value of 0.0487 for PD (SMD 0.29 95% Cl 0.00-0.59). In AD patients, statistical significance (for random effect) was also observed for IL-1β, where higher values of this cytokine were recorded in patients compared to controls (p-value <0.001). In turn, in patients with PD, apart from IL-6, statistical significance was also observed for tumor necrosis factor-α (TNF-α) (p= 0.0431, SMD 0.52 95%Cl 0.02-1.02). Significant heterogeneity was also recorded (Q =85.48; P < 0.01; I = 87%). In both study groups, significant differences in common effect were observed for the anti-inflammatory cytokine IL-10, which could suggest a protective effect of this cytokine in patients with neurodegenerative diseases. The obtained results reinforce the existing clinical evidence that Alzheimer's and Parkinson's diseases are accompanied by an inflammatory response, with considerably higher blood levels observed for pro-inflammatory cytokines: IL-6, TNF-α and IL-1β.
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http://dx.doi.org/10.14336/AD.2024.1174 | DOI Listing |
Neuropharmacology
January 2025
Dept. of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy. Electronic address:
The central nervous system is a well-known steroidogenic tissue producing, among others, cholesterol metabolites such as neuroactive steroids, oxysterols and steroid hormones. It is well known that these endogenous molecules affect several receptor classes, including ionotropic GABAergic and NMDA glutamatergic receptors in neurons. It has been shown that also ionotropic purinergic (P2X) receptors are cholesterol metabolites' targets.
View Article and Find Full Text PDFAging Dis
December 2024
Department of Applied and Clinical Physiology, Collegium Medicum University of Zielona Gora, Zielona Gora, Poland.
Neuroinflammation plays a critical role in Alzheimer's (AD) and Parkinson's diseases (PD) onset, pathophysiology, and progression. The aim of our meta-analysis was to review the available literature to assess the role of neuroinflammation in the pathogenesis of the two most common neurological diseases: Parkinson's disease and Alzheimer's disease. Two medical databases were searched: Web of Science and PubMed in the period from 2009-2023, where a total of 37 publications that met the inclusion criteria were selected for further evaluation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Gladstone Institutes, UCSF, San Francisco, CA, USA.
Background: Cerebrovascular alterations and innate immune activation are key features of Alzheimer's disease (AD). However, the mechanisms that link blood-brain barrier disruption to neurodegeneration are poorly understood and well-defined druggable targets at the neurovascular interface are limited.
Method: By developing a multiomic and genetic loss-of-function pipeline, we reported the transcriptomic and global phosphoproteomic landscape of blood-induced microglia activation and the causal role for fibrin in induction of neurodegenerative genes and oxidative stress pathways in innate immune cells.
Alzheimers Dement
December 2024
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Alzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Background: A case study on a PSEN1 (E280A) carrier with APOECh (R136S) mutation revealed changes in APOE protein function led to a protective effect on AD outcomes. Notably, there is an intriguing disparity between the two hallmark pathologies: a reduction in tauopathy but no change in plaque burden. Given that the APOE protein is predominantly produced by astrocytes and activated microglia, and the APOE gene is among the disease-associated microglia (DAM) genes, it is conceivable that the variance in pathological outcomes may be rooted in the glial response.
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