Background: Deposits of Aβ in brain parenchyma and cerebral vessels are the pathological hallmarks of Alzheimer’s disease (AD). Recently, we demonstrated that aged Alzheimer transgenic mice (APP23), which develop amyloid-β deposits in the brain parenchyma and cerebral vessels, have pre-activated platelets in blood and enhanced integrin activation upon agonist stimulation. Moreover, platelets adhere to vascular amyloid-β deposits and cause vessel occlusion in aged APP23 mice. A comprehensive analysis of these AD transgenic mice revealed that activated platelets directly contribute to vascular amyloid plaques by promoting the formation of Aβ aggregates.

Aims: Investigation of initial changes of platelets from middle-aged transgenic APP23 mice (at the age of 7 to 10 month), which already have amyloid pathology in the brain parenchyma, but still no vascular amyloid deposits.

Methods: FACS analysis and in vitro platelet function.

Results: Middle-aged transgenic APP23 mice had unaltered platelet count, platelet size and glycoprotein expression comparable to control mice. However, transmission electron microscopy analysis showed a significantly increased number of dense granules. The number of α-granules was increased only by trend using platelets from middle-aged APP23 mice. Secretion of α- and dense-granules was increased selectively upon stimulation with CRP that stimulates the major platelet collagen receptor glycoprotein (GP) VI. Additionally, we observed enhanced CRP-triggered aggregation of platelets from middle aged APP23. Flow chamber experiments revealed increased thrombus formation on collagen at high shear rates (1.700 sec-1) ex vivo but unaltered formation of thrombi under moderate shear of 1000 s-1. However, the binding of vWF to platelets was unaltered in APP23 transgenic platelets.

Conclusions: APP23 mice show morphological and functional alterations of platelets before vascular amyloid plaques develop in these mice indicating that platelet changes in aged APP23 mice are not only the result of vascular Aβ deposits. Thus, anti-platelet therapy of AD has to start as early as possible.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/morphological-and-functional-alterations-of-platelets-from-transgenic-app23-mice-at-early-alzheimer-disease-state/