Platelets from early-stage Alzheimer patients show enhanced amyloid binding, an elevated open canalicular system and sex-specific differences in their activation profile

Introduction: Alzheimers disease (AD) is associated with neurodegeneration and dementia. The clinical parameters include the deposition of amyloid-beta into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA). Currently, beta-amyloid-antibodies are emerging as possible therapy for AD. Several biomarkers, such as beta-Amyloid and tau-protein have gained significant value for diagnosing early AD. However, these biomarkers require cerebrospinal fluid. Blood tests for screening of AD are urgently needed. Methods: Patients diagnosed with early AD were analyzed for extracellular amyloid-beta binding to platelets, platelet morphology and platelet activation and compared to age-matched controls. Results: Beside unaltered platelet number and size, we detected increased binding of amyloid-beta to activated platelets isolated from AD patients. Electron microscopy revealed an altered platelet morphology in AD patients including the number of dense granules and the area of the open canalicular system (OCS) as compared to controls. While only minor differences in platelet activation were detected between patients and controls, a significant reduction of integrin alphaIIbbeta3 (fibrinogen receptor) activation was evident in platelets from female compared to male AD patients as determined by flow cytometry. Conclusion: The here presented results emphasize the importance to increase our understanding how platelets contribute to AD pathology in patients in a sex-specific manner. Furthermore, platelet parameters might serve as an ideal biomarker for a first prognosis of AD because platelets can be easily accessed by blood samples. These parameters might include a sex-specific platelet activation profile, the capability to bind Abeta to the platelet surface and the dimension of the OCS by electron microscopy.