The disruption of key mechanisms involved in amyloid beta (Aβ) clearance during the early stages of dementia may contribute to the progression of cognitive decline toward irreversible brain damage. In Show more
The disruption of key mechanisms involved in amyloid beta (Aβ) clearance during the early stages of dementia may contribute to the progression of cognitive decline toward irreversible brain damage. In this study, we investigated multiple immune-related pathways implicated in the management and clearance of Aβ within circulating extracellular vesicles (cEVs) and serum from individuals with subjective cognitive decline (SCD) who later progressed to mild cognitive impairment (MCI). A cytokine panel and the levels of Aβ In SCD patients, the concentrations of Aβ Our findings support the potential value of integrating serum M-CSF levels with RAVLT performance and cEVs Aβ Show less
Methylglyoxal (MG) and glyoxal (GO) are suggested to be associated with the development of neurodegenerative pathologies. However, their peripheral levels in relation to cognitive decline and their ef Show more
Methylglyoxal (MG) and glyoxal (GO) are suggested to be associated with the development of neurodegenerative pathologies. However, their peripheral levels in relation to cognitive decline and their effects on key factors in neuronal cells are poorly investigated. The aim of this study was to determine their serum levels in MCI (mild cognitive impairment) and Alzheimer's disease (AD) patients, to analyze their effects on the neurotrophic and inflammatory factors, on neurodegenerative markers in neuronal cells and in neuronal derived-extracellular vesicles (nEVs). Our results show that MG and GO levels in serum, determined by HPLC, were higher in MCI. ROC (receiver-operating characteristic curves) analysis showed that the levels of MG in serum have higher sensitivity to differentiate MCI from controls but not from AD. Meanwhile, serum GO levels differentiate MCI from control and AD groups. Cells and nEVs levels of BDNF, PRGN, NSE, APP, MMP-9, ANGPTL-4, LCN2, PTX2, S100B, RAGE, Aβ peptide, pTau T181 and alpha-synuclein were quantified by luminex assay. Treatment of neuronal cells with MG or GO reduced the cellular levels of NSE, PRGN, APP, MMP-9 and ANGPTL-4 and the nEVs levels of BDNF, PRGN and LCN2. Our findings suggest that targeting MG and GO may be a promising therapeutic strategy to prevent or delay the progression of AD. Show less