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bonnar-et-al-2023-apoe4-expression-confers-a-mild-persistent-reduction-in-neurovascular-function-in-the-visual-cortex.pdf (2.65 MB)

APOE4 expression confers a mild, persistent reduction in neurovascular function in the visual cortex and hippocampus of awake mice

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Version 2 2023-08-09, 14:42
Version 1 2023-06-10, 07:05
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posted on 2023-08-09, 14:42 authored by Orla Bonnar, Kira ShawKira Shaw, Silvia Anderle, Dorieke Grijseels, Devin Clarke, Laura Bell, Sarah KingSarah King, Catherine HallCatherine Hall

Vascular factors are known to be early and important players in Alzheimer’s disease (AD) development, however the role of the ε4 allele of the Apolipoprotein (APOE) gene (a risk factor for developing AD) remains unclear. APOE4 genotype is associated with early and severe neocortical vascular deficits in anaesthetised mice, but in humans, vascular and cognitive dysfunction are focused on the hippocampal formation and appear later. How APOE4 might interact with the vasculature to confer AD risk during the preclinical phase represents a gap in existing knowledge. To avoid potential confounds of anaesthesia and to explore regions most relevant for human disease, we studied the visual cortex and hippocampus of awake APOE3 and APOE4-TR mice using 2-photon microscopy of neurons and blood vessels. We found mild vascular deficits: vascular density and functional hyperaemia were unaffected in APOE4 mice, and neuronal or vascular function did not decrease up to late middle-age. Instead, vascular responsiveness was lower, arteriole vasomotion was reduced and neuronal calcium signals during visual stimulation were increased. This suggests that, alone, APOE4 expression is not catastrophic but stably alters neurovascular physiology. We suggest this state makes APOE4 carriers more sensitive to subsequent insults such as injury or beta amyloid accumulation.

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Publication status

  • Published

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  • Published version

Journal

Journal of Cerebral Blood Flow and Metabolism

ISSN

0271-678X

Publisher

SAGE

Department affiliated with

  • Psychology Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2023-05-19

First Open Access (FOA) Date

2023-05-19

First Compliant Deposit (FCD) Date

2023-05-18

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