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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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
Number of pages9
JournalCellular Signalling
Volume28
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

Fingerprint

Alzheimer Disease
Thrombosis
Blood Platelets
Vascular Diseases
Fibrillar Collagens
Myosin-Light-Chain Kinase
Vascular Dementia
Aptitude
von Willebrand Factor
Hypercholesterolemia
Hemostasis
Phosphatidylinositol 3-Kinases
Amyloid
Integrins
Protein-Tyrosine Kinases
Fibrinogen
Disease Progression
Atherosclerosis
Glycoproteins
Phosphotransferases

Keywords

  • Adhesion
  • Alzheimer's disease
  • Amyloid
  • Platelets
  • Thrombus formation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Increased platelet adhesion and thrombus formation in a mouse model of Alzheimer's disease. / Canobbio, Ilaria; Visconte, Caterina; Oliviero, Barbara; Guidetti, Gianni; Zarà, Marta; Pula, Giordano; Torti, Mauro.

In: Cellular Signalling, Vol. 28, No. 12, 01.12.2016, p. 1863-1871.

Research output: Contribution to journalArticle

Canobbio, I, Visconte, C, Oliviero, B, Guidetti, G, Zarà, M, Pula, G & Torti, M 2016, 'Increased platelet adhesion and thrombus formation in a mouse model of Alzheimer's disease', Cellular Signalling, vol. 28, no. 12, pp. 1863-1871. https://doi.org/10.1016/j.cellsig.2016.08.017
Canobbio, Ilaria ; Visconte, Caterina ; Oliviero, Barbara ; Guidetti, Gianni ; Zarà, Marta ; Pula, Giordano ; Torti, Mauro. / Increased platelet adhesion and thrombus formation in a mouse model of Alzheimer's disease. In: Cellular Signalling. 2016 ; Vol. 28, No. 12. pp. 1863-1871.
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