Abstract
STRUCTURED ABSTRACTBACKGROUNDAlzheimer’s disease (AD) is the most common cause of dementia worldwide, with apolipoprotein ε4 (APOEε4) being the strongest genetic risk factor. Current clinical diagnostic imaging focuses on amyloid and tau; however, new methods are needed for earlier detection.METHODSPET imaging of18F-FDG and64Cu-PTSM was used to assess metabolism-perfusion profiles in both sexes of aging C57BL/6J, andAPOEε3/ε3, APOEε4/ε4, andAPOEε3/ε4.RESULTSAcross all strains, 8 months is a key transition stage. Females exhibited the greatest number of regional changes for both tracers, which correlate with GO-term enrichments for glucose metabolism, perfusion and immunity. Our neurovascular uncoupling analysis revealedAPOEε4/ε4exhibited significant Type-1 uncoupling at 8 and 12 months, whileAPOEε3/ε4demonstrated significant Type-2 uncoupling by 8 months.DISCUSSIONThis work highlightsAPOEε4status determines key differences in progression to neurovascular uncoupling. Our method detects changes in neurovascular coupling, and may serve as an early diagnostic biomarker.
Publisher
Cold Spring Harbor Laboratory