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

TL;DR

Alzheimer's disease transgenic mice show reduced heart function after heart attack due to altered platelet activation and collagen changes.

Contribution

The study reveals a link between Alzheimer's pathology and worsened cardiac outcomes after myocardial infarction in a mouse model.

Findings

APP23 mice showed significantly decreased left ventricular function after myocardial infarction compared to controls.

Altered collagen composition in scar tissue and increased platelet degranulation were observed in APP23 mice.

Findings suggest Alzheimer's patients may face higher cardiac risk after heart attacks.

Abstract

Background: Neurodegeneration and dementia are key factors in Alzheimer’s disease (AD). The deposition of amyloid-ß 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. However, the underlying mechanisms and the consequences of AMI in AD patients are unclear to date. Methods: AD transgenic APP23 mice were analyzed in experimental AMI using the closed-chest model. Results: APP23 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. 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. Conclusions: These results suggest that AD patients are at higher risk for cardiac damage after AMI. This implies the need for a personalized therapy of AMI in AD patients.

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