Brain aerobic glycolysis and resilience in Alzheimer disease

Goyal, M. S.; Blazey, T.; Metcalf, N.; McAvoy, M. P.; Strain, J.; Rahmani, M.; Durbin, T.; Xiong, C.; Benzinger, T. L. S.; Morris, J. C.; Raichle, M. E.; Vlassenko, A. G.

doi:10.1101/2022.06.21.497006

bioRxiv · 10.1101/2022.06.21.497006

Brain aerobic glycolysis and resilience in Alzheimer disease

Goyal, M. S.·Blazey, T.·Metcalf, N.·McAvoy, M. P.·Strain, J.·Rahmani, M.·Durbin, T.·Xiong, C.·Benzinger, T. L. S.·Morris, J. C.·Raichle, M. E.·Vlassenko, A. G.

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Abstract

The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (A{beta}) deposition in individuals with dementia of the Alzheimer type (DAT) and asymptomatic individuals with brain amyloid deposition. Brain AG decreases with age but the functional significance of this decrease with regard to the development of DAT symptomatology is poorly understood. Using PET measurements of regional blood flow, oxygen consumption and glucose utilization--from which we derive AG--we find that cognitive impairment is strongly associated with loss of the typical youthful pattern of AG. In contrast, amyloid positivity without cognitive impairment was associated with preservation of youthful brain AG, which was even higher than that seen in typical, cognitively unimpaired, amyloid negative adults. Similar findings were not seen for blood flow nor oxygen consumption. Finally, in cognitively unimpaired adults, white matter hyperintensity burden was found to be specifically associated with decreased youthful brain AG. Our results implicate preserved AG as a factor in brain resilience to amyloid pathology and suggest that white matter disease may be a cause and/or consequence of this impaired resilience.

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Goyal, M. S., Blazey, T., Metcalf, N., McAvoy, M. P., Strain, J., Rahmani, M., Durbin, T., Xiong, C., Benzinger, T. L. S., Morris, J. C., Raichle, M. E., Vlassenko, A. G.. 2022-06-23. Brain aerobic glycolysis and resilience in Alzheimer disease. https://doi.org/10.1101/2022.06.21.497006

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