Assessment of Neurovascular Uncoupling: APOE Status is a Key Driver of Early Metabolic and Vascular Dysfunction
| dc.contributor.author | Onos, Kristen | |
| dc.contributor.author | Lin, Peter B. | |
| dc.contributor.author | Pandey, Ravi S. | |
| dc.contributor.author | Persohn, Scott A. | |
| dc.contributor.author | Burton, Charles P. | |
| dc.contributor.author | Miner, Ethan W. | |
| dc.contributor.author | Eldridge, Kierra | |
| dc.contributor.author | Nyandu Kanyinda, Jonathan | |
| dc.contributor.author | Foley, Kate E. | |
| dc.contributor.author | Carter, Gregory W. | |
| dc.contributor.author | Howell, Gareth R. | |
| dc.contributor.author | Territo, Paul R. | |
| dc.contributor.department | Neurology, School of Medicine | |
| dc.date.accessioned | 2024-05-22T09:06:45Z | |
| dc.date.available | 2024-05-22T09:06:45Z | |
| dc.date.issued | 2024-03-13 | |
| dc.description.abstract | Background: Alzheimer'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. 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 APOEε4/ε4 exhibited significant Type-1 uncoupling (↓ glucose uptake, ↑ perfusion) at 8 and 12 mo, while APOEε3/ε4 demonstrated Type-2 uncoupling (↑ glucose uptake, ↓ perfusion), while immunopathology confirmed cell specific contributions. Discussion: This work highlights APOEε4 status in AD progression manifest as neurovascular uncoupling driven by immunological activation, and may serve as an early diagnostic biomarker. | |
| dc.eprint.version | Pre-Print | |
| dc.identifier.citation | Onos K, Lin PB, Pandey RS, et al. Assessment of Neurovascular Uncoupling: APOE Status is a Key Driver of Early Metabolic and Vascular Dysfunction. Preprint. bioRxiv. 2024;2023.12.13.571584. Published 2024 Mar 13. doi:10.1101/2023.12.13.571584 | |
| dc.identifier.uri | https://hdl.handle.net/1805/40917 | |
| dc.language.iso | en_US | |
| dc.publisher | bioRxiv | |
| dc.relation.isversionof | 10.1101/2023.12.13.571584 | |
| dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.source | PMC | |
| dc.subject | APOE | |
| dc.subject | Alzheimer’s disease | |
| dc.subject | Metabolism | |
| dc.subject | Perfusion | |
| dc.subject | Uncoupling | |
| dc.title | Assessment of Neurovascular Uncoupling: APOE Status is a Key Driver of Early Metabolic and Vascular Dysfunction | |
| dc.type | Article |