Increased platelet adhesion and thrombus formation in a mouse model of Alzheimer's disease.
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.
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy. Electronic address: ilaria.canobbio@unipv.it.
Ilaria
I
Canobbio
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
Caterina
C
Visconte
Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
Barbara
B
Oliviero
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
Gianni
G
Guidetti
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
Marta
M
Zarà
Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom.
Giordano
G
Pula
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
Mauro
M
Torti
D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications / Q000473:pathology*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008822:Mice, Transgenic; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D015398:Signal Transduction; D013927:Thrombosis / Q000150:complications* / Q000473:pathology*
D006023:Glycoproteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
Adhesion; Alzheimer's disease; Amyloid; Platelets; Thrombus formation