Background: Neuroinflammation, with altered peripheral proinflammatory cytokine production, plays a major role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), while the role of inflammation in dementia with Lewy bodies (DLB) is less known and the results of different studies are often in disagreement.Objective: The present study aimed to investigate the levels of TNF alpha and IL-6 in serum and supernatants, and the related DNA methylation in patients affected by DLB and AD compared to healthy controls (HCs), to clarify the role of epigenetic mechanisms of DNA promoter methylation on of pro-inflammatory cytokines overproduction.Methods: Twenty-one patients with DLB and fourteen with AD were frequency-matched for age and sex with eleven HCs. Clinical evaluation, TNF alpha and IL-6 gene methylation status, cytokine gene expression levels and production in serum and peripheral blood mononuclear cell (PBMC) supernatants were performed.Results: In AD and DLB patients, higher serum levels of IL-6 and TNF alpha were detected than in HCs. Differences in LPS-stimulated versus spontaneous PBMCs were observed between DLB, AD, and HC in the levels of TNF alpha (p = 0.027) and IL-6 (p < 0.001). Higher levels were also revealed for sIL-6R in DLB (p < 0.001) and AD (p < 0.001) in comparison with HC.DNA hypomethylation in IL-6 and TNF alpha CpG promoter sites was detected for DLB and AD patients compared to the corresponding site in HCs.Conclusions: Our preliminary study documented increased levels of IL-6 and TNF alpha in DLB and AD patients to HCs. This overproduction can be due to epigenetic mechanisms regarding the hypomethylation of DNA promoters.
Search in the Periphery for Potential Inflammatory Biomarkers of Dementia with Lewy Bodies and Alzheimer's Disease
Pilotto, Andrea;Padovani, Alessandro;
2024-01-01
Abstract
Background: Neuroinflammation, with altered peripheral proinflammatory cytokine production, plays a major role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), while the role of inflammation in dementia with Lewy bodies (DLB) is less known and the results of different studies are often in disagreement.Objective: The present study aimed to investigate the levels of TNF alpha and IL-6 in serum and supernatants, and the related DNA methylation in patients affected by DLB and AD compared to healthy controls (HCs), to clarify the role of epigenetic mechanisms of DNA promoter methylation on of pro-inflammatory cytokines overproduction.Methods: Twenty-one patients with DLB and fourteen with AD were frequency-matched for age and sex with eleven HCs. Clinical evaluation, TNF alpha and IL-6 gene methylation status, cytokine gene expression levels and production in serum and peripheral blood mononuclear cell (PBMC) supernatants were performed.Results: In AD and DLB patients, higher serum levels of IL-6 and TNF alpha were detected than in HCs. Differences in LPS-stimulated versus spontaneous PBMCs were observed between DLB, AD, and HC in the levels of TNF alpha (p = 0.027) and IL-6 (p < 0.001). Higher levels were also revealed for sIL-6R in DLB (p < 0.001) and AD (p < 0.001) in comparison with HC.DNA hypomethylation in IL-6 and TNF alpha CpG promoter sites was detected for DLB and AD patients compared to the corresponding site in HCs.Conclusions: Our preliminary study documented increased levels of IL-6 and TNF alpha in DLB and AD patients to HCs. This overproduction can be due to epigenetic mechanisms regarding the hypomethylation of DNA promoters.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
