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bioRxiv · 10.1101/2025.09.04.674210

Elevated IL-1 beta plasma levels, altered platelet activation and cardiac remodeling lead to moderately decreased LV function in Alzheimer transgenic mice after myocardial ischemia and reperfusion

Donner, L.·Gorressen, S.·Fischer, J.·Elvers, M.
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Abstract

IntroductionNeurodegeneration and dementia are key factors in Alzheimers disease (AD). The deposition of amyloid-{beta} into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA) are the main clinical parameters of AD. Acute myocardial infarction (AMI) and AD share a comparable pathophysiology. In detail, AMI survivors have a higher risk of vascular dementia and AD patients with AMI face a poor prognosis with a high rate of major adverse cardiovascular events. High blood levels of amyloid-{beta}40 are identified in patients with high risk for cardiovascular death. However, the underlying mechanisms and the consequences of AMI in AD patients are unclear to date. MethodsAD transgenic APP23 mice were analysed in an experimental AMI using the closed-chest model. ResultsAPP23 mice displayed significantly decreased left ventricular function as detected by FS/MPI (fractional shortening/myocardial performance index) after 24 h and 3 weeks after ligation of the LAD compared to WT controls. No differences have been observed in infarct and scar size. However, the analysis of cardiac remodeling after 3 weeks showed an altered composition of the collagen tissue of the scar with elevated tight but reduced fine collagen in APP23 mice. Altered scar formation was accompanied by elevated degranulation of platelets following activation of the collagen receptor GPVI. ConclusionThe here presented results suggest that AD patients are at higher risk for cardiac damage after AMI that might increase the risk for cardiovascular death. This implies the need of a personalized therapy of AMI in AD patients.

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Donner, L., Gorressen, S., Fischer, J., Elvers, M.. 2025-09-09. Elevated IL-1 beta plasma levels, altered platelet activation and cardiac remodeling lead to moderately decreased LV function in Alzheimer transgenic mice after myocardial ischemia and reperfusion. https://doi.org/10.1101/2025.09.04.674210

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