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Updated: Jun 27, 2026

Non-invasive Assessment of Microvascular and Endothelial Function
Published on: January 29, 2013
Assessment of Neurovascular Uncoupling: APOE Status is a Key Driver of Early Metabolic and Vascular Dysfunction
Kristen Onos1, Peter B Lin2,3, Ravi S Pandey4
1The Jackson Laboratory, Bar Harbor, ME 04609 USA.
Background:
Alzheimer's disease (AD) is the most common cause of dementia worldwide, with apolipoprotein ε4 (APOE) being the strongest genetic risk factor. Current clinical diagnostic imaging focuses on amyloid and tau; however, new methods are needed for earlier detection.
Methods:
PET imaging was used to assess metabolism-perfusion in both sexes of aging C57BL/6J, and hAPOE mice, and were verified by transcriptomics, and immunopathology.
Results:
All hAPOE strains showed AD phenotype progression by 8 mo, with females exhibiting the regional changes, which correlated with GO-term enrichments for glucose metabolism, perfusion, and immunity. Uncoupling analysis revealed APOE exhibited significant Type-1 uncoupling (↓ glucose uptake, ↑ perfusion) at 8 and 12 mo, while APOE demonstrated Type-2 uncoupling (↑ glucose uptake, ↓ perfusion), while immunopathology confirmed cell specific contributions.
Discussion:
This work highlights APOE status in AD progression manifest as neurovascular uncoupling driven by immunological activation, and may serve as an early diagnostic biomarker.
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