Increased platelet adhesion and thrombus formation in a mouse model of Alzheimer's disease

Ilaria Canobbio, Caterina Visconte, Barbara Oliviero, Gianni Guidetti, Marta Zara, Giordano Pula, Mauro Torti

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Abstract

Vascular dysfunctions and Alzheimer's disease show significant similarities and overlaps. Cardiovascular risk factors (hypercholesterolemia, hypertension, obesity, atherosclerosis and diabetes) increase the risk of vascular dementia and Alzheimer's disease. Conversely, Alzheimer's patients have considerably increased predisposition of ischemic and hemorrhagic strokes. Platelets are major players in haemostasis and thrombosis and are involved in inflammation. We have investigated morphology and function of platelets in 3xTg-AD animals, a consolidate murine model for Alzheimer's disease. Platelets from aged 3xTg-AD mice are normal in number and glycoprotein expression, but adhere more avidly on matrices such as fibrillar collagen, von Willebrand factor, fibrinogen and amyloid peptides compared to platelets from age-matching wild type mice. 3xTg-AD washed platelets adherent to collagen also show increased phosphorylation of selected signaling proteins, including tyrosine kinase Pyk2, PI3 kinase effector Akt, p38MAP kinase and myosin light chain kinase, and increased ability to form thrombi under shear. In contrast, aggregation and integrin αIIbβ3 activation induced by several agonists in 3xTg-AD mice are similar to wild type platelets. These results demonstrated that Alzheimer's mutations result in a significant hyper-activated state of circulating platelets, evident with the progression of the disease.
Original languageEnglish
Pages (from-to)1863-1871
JournalCellular Signalling
Volume28
Issue number12
Early online date1 Sep 2016
DOIs
Publication statusPublished - Dec 2016

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    Canobbio, I., Visconte, C., Oliviero, B., Guidetti, G., Zara, M., Pula, G., & Torti, M. (2016). Increased platelet adhesion and thrombus formation in a mouse model of Alzheimer's disease. Cellular Signalling, 28(12), 1863-1871. https://doi.org/10.1016/j.cellsig.2016.08.017