Evidence that a metabolic shift towards glyclyosis in PBMCs may provide the basis of a biomarker of early cognitive dysfunction

Wolfe, Hannah, O'Sullivan, Michael, Hannigan, Caoimhe, Brennan, Sabina, Lawlor, Brian A., Robertson, Ian H. and Lynch, Marina (2017) Evidence that a metabolic shift towards glyclyosis in PBMCs may provide the basis of a biomarker of early cognitive dysfunction. Alzheimer's & Dementia, 13 (7). P982-P983. ISSN 1552-5260

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Abstract

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.

Item Type:	Article
Subjects:	B Philosophy. Psychology. Religion > Psychology B Philosophy. Psychology. Religion > Psychology > Cognitive psychology
Divisions:	School of Business > Staff Research and Publications
Depositing User:	Caoimhe Ní Mhaicín
Date Deposited:	24 Sep 2018 13:46
Last Modified:	24 Sep 2018 13:46
URI:	https://norma.ncirl.ie/id/eprint/3191

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