Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 317, Issue -, Pages 24-31Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2018.02.007
Keywords
Inflammatory cytokines; Chemokines; Cognitive function; Peripheral blood mononuclear cells (PBMCs); Monocyte-derived macrophages (MDMs); Glycolysis; Metabolism; PFKFB3
Categories
Funding
- Government of Ireland Postgraduate Scholarship (Irish Research Council) [GOIPG/2013/331]
- Science Foundation Ireland [15/iA/3052]
- Science Foundation Ireland (SFI) [15/IA/3052] Funding Source: Science Foundation Ireland (SFI)
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Identification of a blood-based biomarker that can detect early cognitive decline presents a significant healthcare challenge. We prepared peripheral blood mononuclear cells (PBMCs) from individuals who had a poorer than predicted performance in their delayed recall performance on the Logical Memory II Subtest of the Wechsler Memory Scale (WMS) relative to their IQ estimated by the National Adult Reading Test (NART); we described these individuals as IQ-discrepant, compared with IQ-consistent, individuals. Stimulation with A beta + LPS increased production of TNF alpha to a greater extent in cells from IQ-discrepant, compared with IQ-consistent, individuals. This was associated with a shift towards glycolysis and the evidence indicates that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3 plays a role in driving glycolysis. A similar shift towards glycolysis was observed in MDMs prepared from IQ-discrepant, compared with IQ-consistent, individuals. The important finding here is that we have established an increased sensitivity to A beta + LPS stimulation in PBMCs from individuals that under-perform on a memory task, relative to their estimated premorbid IQ, which may be an indicator of early cognitive decline. This may be a useful tool in determining the presence of early cognitive dysfunction.
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