HAI Book 2025 - Flipbook - Page 231
Adams, Jenna
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Metabolic inefficiency is associated with regional vulnerability to tau
deposition
Jenna Adams1, Dana Parker1, Irene Zhao1, Michael Yassa1
1
University of California, Irvine, Irvine, CA, US
Background: Increased metabolic demand may predispose brain regions to the accumulation of pathology in
Alzheimer9s disease. Here, we tested if metabolic inefficiency is associated with regional patterns of tau
deposition in older adults.
Methods: We characterized patterns of glucose metabolism using 18F-Fluorodeoxyglucose-PET (FDG) in relation
to structural connectivity and tau deposition in older adults from ADNI. 482 FDG scans were warped to MNI space.
The mean SUVR of 218 cortical ROIs from the Brainnetome Atlas were extracted and averaged across cognitively
normal participants (Fig1A). Multishell diffusion MRI from 40 cognitively normal, amyloid-negative participants was
used to create whole brain tractograms. The average number of streamlines between each ROI pair was extracted
to create a healthy structural connectome. The density of structural connections to each region, normalized by
regional volume, was computed (Fig1B). The ratio of mean FDG SUVR to the density of structural connections was
calculated for each region and used as a measure of metabolic demand, with higher values representing
inefficiency (higher FDG than expected for structural density). 18F-Flortaucipir SUVR was averaged across 1,628
scans across diagnoses to obtain regional patterns of tau-PET uptake.
Results: Regions demonstrating the greatest metabolic inefficiency (top 5% of regions) were primarily found
within the medial temporal lobe, including the transentorhinal/perirhinal cortex, entorhinal cortex, temporal
agranular cortex, and amygdala (Fig1C). We next tested associations between metabolic inefficiency and regional
vulnerability to tau deposition. Metabolic inefficiency values were highest for regions classified within earlier
Braak stages (r = 0.39, p
