Document Type
Article
Publication Date
7-1-2024
Original Citation
Onos KD,
Lin P,
Pandey R,
Persohn S,
Burton C,
Miner E,
Eldridge K,
Kanyinda J,
Foley K,
Carter GW,
Howell G,
Territo P.
Assessment of neurovascular uncoupling: APOE status is a key driver of early metabolic and vascular dysfunction. Alzheimers Dement. 2024;20(7):4951-69.
Keywords
JGM, JMG, SS1, Animals, Female, Male, Mice, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Brain, Disease Models, Animal, Disease Progression, Glucose, Mice, Inbred C57BL, Mice, Transgenic, Neurovascular Coupling, Positron-Emission Tomography
JAX Source
Alzheimers Dement. 2024;20(7):4951-69.
ISSN
1552-5279
PMID
38713704
DOI
https://doi.org/10.1002/alz.13842
Grant
NIH/NIA, Grant/Award Numbers: U54-AG054345, U54-AG054349, R21-AG078575-01
Abstract
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia worldwide, with apolipoprotein Eε4 (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 months, 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 months, 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 manifests as neurovascular uncoupling driven by immunological activation, and may serve as an early diagnostic biomarker.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.