Type

Journal Article

Authors

Marina Lynch
Ian H Robertson
Brian A. Lawlor
Sabina Brennan
Caoimhe Hannigan
Michael O'Sullivan
Hannah Wolfe

Subjects

Psychology

Topics
tumour necrosis factor tnf cognitive psychology cognitive function il 10 mrna expression older adults kinase 3 psychology

Evidence that a metabolic shift towards glyclyosis in PBMCs may provide the basis of a biomarker of early cognitive dysfunction (2017)

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.
Collections Ireland -> National College Ireland -> Status = Published
Ireland -> National College Ireland -> Subject = B Philosophy. Psychology. Religion: Psychology: Cognitive psychology
Ireland -> National College Ireland -> Subject = B Philosophy. Psychology. Religion
Ireland -> National College Ireland -> Type = Article
Ireland -> National College Ireland -> Subject = B Philosophy. Psychology. Religion: Psychology

Full list of authors on original publication

Marina Lynch, Ian H Robertson, Brian A. Lawlor, Sabina Brennan, Caoimhe Hannigan, Michael O'Sullivan, Hannah Wolfe

Experts in our system

1
Marina Annetta Lynch
Trinity College Dublin
Total Publications: 80
 
2
Ian H Robertson
Trinity College Dublin
Total Publications: 162
 
3
Brian A. Lawlor
National College Ireland
Total Publications: 125
 
4
Sabina Brennan
National College Ireland
Total Publications: 47
 
5
Caoimhe Hannigan
National College Ireland
Total Publications: 58
 
6
Michael O'Sullivan
National College Ireland
Total Publications: 12
 
7
Hannah Wolfe
National College Ireland
Total Publications: 7