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

TL;DR

Platelets from early Alzheimer's patients show unique features like increased amyloid binding and sex-specific activation differences, suggesting potential blood-based biomarkers.

Contribution

Identifies platelet-specific sex differences and novel platelet biomarkers for early Alzheimer's detection.

Findings

Platelets from Alzheimer's patients show increased surface APP/Aβ immunoreactivity.

Female AD patients have reduced integrin αIIbβ3 activation compared to males.

Altered open canalicular system in AD patient platelets was observed via electron microscopy.

Abstract

Alzheimer's disease (AD) is associated with neurodegeneration and dementia. Key clinical hallmarksinclude the deposition of amyloid-ß (Aβ) into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA). Currently, anti-Aß antibodies are emerging as possible therapy for AD. Several biomarkers, such as Aß and tau-protein have gained diagnostic relevance for early AD; however, their assessment requires cerebrospinal fluid. Therefore, blood-based biomarkers for AD screening are urgently needed.

Patients diagnosed with early AD were analyzed for extracellular Aß binding to platelets, platelet morphology and platelet activation, and were compared with age-matched controls.

Platelet number and size were unaltered between groups. However, platelets isolated from AD patients exhibited increased surface APP/Aβ immunoreactivity compared with age-matched controls. Transmission electron microscopy revealed altered platelet morphology in AD patients, including changes in the number of dense granules and an increased area of the open canalicular system (OCS). While only minor differences in platelet activation were detected between patients and controls, a significant reduction in integrin αIIbβ3 (fibrinogen receptor) activation was observed in platelets from female compared to male AD patients, as determined by flow cytometry.

The results presented here emphasize the importance of understanding whether platelets contribute to AD pathology in a sex-specific manner. Furthermore, platelet parameters may serve as promising biomarker for early AD prognosis, as platelets are easily accessible via blood sampling. These parameters may include sex-specific platelet activation profiles, the ability of platelets to bind APP/Aß at their surface, and OCS dimensions assessed by electron microscopy.

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