Monocytes exposed to plasma from patients with Alzheimer's disease undergo metabolic reprogramming. (November 2019)

• Record Type: Journal Article
• Authors: Wolfe, Hannah; Mela, Virginia; Minogue, Aedin M.; Miller, Anne-Marie; McGuigan, Chris; Williams, Laura; Lohan, Deirdre; Lawlor, Brian A.; Lynch, Marina A.
• Is Part Of: Neuroscience research. Volume 148(2019)
• Page Start: 54
• Page End: 60
• Publication Date: 2019-11
• Subjects: Alzheimer's disease -- MCI -- APP/PS1 mice -- Plasma -- J774.2 cells -- THP-1 cells -- Inflammatory markers -- Glycolysis; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2019.01.001
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: Plasma from APP/PS1 mice induced an inflammatory phenotype in J774.2 cells. This was accompanied by increased glycolysis in J774.2 cells. Plasma from AD, but not MCI patients, increased IL-8 mRNA in THP-1 cells. This was associated with increased glycolysis. The data identifies a means of discriminating between MCI and AD. Abstract: The search for a blood-based biomarker that identifies Alzheimer's disease (AD) and can replace current invasive and expensive diagnostic tests, continues. The most extensively-examined peripheral marker is β-amyloid (Aβ) but the results are inconsistent across studies and do not reflect the changes that take place in the brain. Several studies have assessed possible proteomic signatures but with inconsistent findings, although increases in circulating inflammatory molecules are generally observed. Here, rather than focus on identifying changes in the circulation, we evaluated the effect of plasma from patients with mild cognitive impairment (MCI) and AD on the human monocyte-like cell line, THP-1 cells, and plasma from an AD mouse model on a mouse monocyte-macrophage cell line, J774.2 cells. Plasma from AD patients and the AD mouse model increased inflammatory molecules in the cells and these changes were accompanied by an increase in glycolysis. Interestingly, plasma from MCI patients exerted no significant effect on THP-1 cells. The possibility therefore exists that evaluating the effect of plasma on IL-8 and TNFα mRNA in THP-1 cells combined with analysis of glycolysis in these cells, may be the basis of an indicator that discriminates between AD and MCI and normal controls, but is unlikely to be useful in identifying early pathological changes.