A shift to glycolysis accompanies the inflammatory changes in PBMCs from individuals with an IQ-discrepant memory

Hannah Wolfe, Caoimhe Hannigan, Michael O'Sullivan, Liam Barry Carroll, Sabina Brennan, Brian Lawlor, Ian H. Robertson, Marina Lynch
Journal of Neuroimmunology. 2018-04-01; 317: 24-31
DOI: 10.1016/j.jneuroim.2018.02.007

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Wolfe H(1), Hannigan C(2), O’Sullivan M(2), Carroll LB(1), Brennan S(2), Lawlor
B(1), Robertson IH(2), Lynch M(3).

Author information:
(1)Physiology Department, Trinity College Institute of Neuroscience, Trinity
College, Dublin, Ireland; School of Medicine, Trinity College, Dublin, Ireland.
(2)Physiology Department, Trinity College Institute of Neuroscience, Trinity
College, Dublin, Ireland; School of Psychology, Trinity College, Dublin,
Ireland.
(3)Physiology Department, Trinity College Institute of Neuroscience, Trinity
College, Dublin, Ireland; School of Medicine, Trinity College, Dublin, Ireland.
Electronic address: .

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 Aβ +
LPS increased production of TNFα 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
Aβ + 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.