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[P3–125]: EVIDENCE THAT A METABOLIC SHIFT TOWARDS GLYCOLYSIS IN PBMCS MAY PROVIDE THE BASIS OF A BIOMARKER OF EARLY COGNITIVE DYSFUNCTION
Author(s) -
Wolfe Hannah,
O'Sullivan Michael,
Hannigan Caoimhe,
Brennan Sabina,
Lawlor Brian,
Robertson Ian H.,
Lynch Marina
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1336
Subject(s) - context (archaeology) , wechsler adult intelligence scale , cognition , biomarker , peripheral blood mononuclear cell , population , proinflammatory cytokine , intelligence quotient , inflammation , medicine , tumor necrosis factor alpha , cohort , psychology , oncology , immunology , biology , psychiatry , genetics , paleontology , environmental health , in vitro
Background A major challenge in the context of the increasing aging population is to identify a method of identifying cognitive dysfunction at the earliest possible opportunity, preferably a marker that is blood-based and therefore amenable to assessment on a longitudinal basis. In this study, we identified 2 cohorts of healthy older adults that were classified as IQ-memory consistent (n=47) or IQ-memory discrepant (n=28; IQ-con, IQ-dis) on the basis of their performance in the Wechsler Memory Scale story recall test relative to their performance in the National Adult Reading Test. Methods We cultured THP-1 cells and incubated them for 4h with plasma (1:40) from IQ-con and IQ-dis individuals. Cells were harvested and assessed for mRNA expression of Interleukin (IL)-8 and tumour necrosis factor-α (TNFα). To further explore if the data are indicative of an inflammatory phenotype that is linked with poorer cognitive function, we selected 10 individuals from the IQ-dis cohort with the 10 highest IL-8 mRNA values and 10 IQ-con individuals with the 10 lowest IL-8 mRNA values for further analysis. It has been shown that inflammatory changes in several cell types is associated with a shift in metabolic profile towards glycolysis and, to determine whether any inflammation suggested by our data in IQ-dis individuals was linked with altered metabolism in PBMCs, we stimulated cells with amyloid-β (Aβ) and lipopolysaccharide (LPS) for 24h and assessed changes using a SeahorseXFe24 Analyser. Results The data indicate that both IL-8 and TNFα mRNA were increased in THP-1 cells that were incubated with plasma from IQ-dis, compared with IQ-con, individuals. The data also show that glycolysis in Aβ+LPS stimulated cells was significantly greater in PBMCs from IQ-dis individuals compared with IQ-con individuals. It is known that phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a significant driver of glycolysis because it increases PFKFB1 activity, which converts fructose-6-phosphate to fructose-1, 6-bisphosphate. The data show that PFKFB3 mRNA was also increased in PBMCs from IQ-dis individuals and a significant increase in the ratio of PFKFB3/PFKFB1 was also observed. Conclusions We conclude that the metabolic shift towards glycolysis on PBMCs could represent a potential biomarker assay for the detection of early cognitive decline.