Blood-Based Bioenergetic Profiling Reflects Differences in Brain Bioenergetics and Metabolism

Daniel J Tyrrell, Manish S Bharadwaj, Matthew J Jorgensen, Thomas C Register, Carol Shively, Rachel N Andrews, Bryan Neth, C. Dirk Keene, Akiva Mintz, Suzanne Craft, Anthony J A Molina, Daniel J Tyrrell, Manish S Bharadwaj, Matthew J Jorgensen, Thomas C Register, Carol Shively, Rachel N Andrews, Bryan Neth, C. Dirk Keene, Akiva Mintz, Suzanne Craft, Anthony J A Molina

Abstract

Blood-based bioenergetic profiling provides a minimally invasive assessment of mitochondrial health shown to be related to key features of aging. Previous studies show that blood cells recapitulate mitochondrial alterations in the central nervous system under pathological conditions, including the development of Alzheimer's disease. In this study of nonhuman primates, we focus on mitochondrial function and bioenergetic capacity assessed by the respirometric profiling of monocytes, platelets, and frontal cortex mitochondria. Our data indicate that differences in the maximal respiratory capacity of brain mitochondria are reflected by CD14+ monocyte maximal respiratory capacity and platelet and monocyte bioenergetic health index. A subset of nonhuman primates also underwent [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to assess brain glucose metabolism. Our results indicate that platelet respiratory capacity positively correlates to measures of glucose metabolism in multiple brain regions. Altogether, the results of this study provide early evidence that blood-based bioenergetic profiling is related to brain mitochondrial metabolism. While these measures cannot substitute for direct measures of brain metabolism, provided by measures such as FDG-PET, they may have utility as a metabolic biomarker and screening tool to identify individuals exhibiting systemic bioenergetic decline who may therefore be at risk for the development of neurodegenerative diseases.

Figures

Figure 1
Figure 1
Associations of CD14+ monocyte (a) maximal respiration (pmol/min/250,000 cells) and (b) BHI with the maximal respiratory capacity of frontal cortex mitochondria (pmol/min/5 μg mitochondrial protein). Pearson's correlations and p values for each association are shown.
Figure 2
Figure 2
Association of platelet BHI with the maximal respiratory capacity of frontal cortex mitochondria (pmol/min/5 μg mitochondrial protein). Pearson's correlation and p value are shown.

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