Kurzfassung

Objectives
Alzheimer's disease (AD) is a neurodegenerative disease that is associated with progressive and irreversible memory loss and cognitive decline. There is increasing notion that platelets might contribute to the pathogenesis of AD. Indeed, platelets of AD patients show significant structural and molecular changes compared with those of healthy individuals. However, it is completely unknown if and to what extent platelets in AD are causal in some of the pathological aspects of AD. The aim of this study was to investigate whether platelets from aged APP/PS1 mice, a genetic model of AD pathology, can convey structural and functional deficits in young healthy mice.
Methods
Platelet homogenates derived from 22-month-old mice (WT and APP/PS1) were injected via the tail vein into 3-month-old WT animals over a four-week period. Behavioral tests were conducted to evaluate cognitive function. Brain tissue was used for immunohistochemistry.
Results
Transfusion of old AD platelet homogenate results in structural hippocampal changes in healthy young mice. The hippocampal expression of pCreb as well as NeuN is reduced, and a higher expression of Casp3 can be observed, indicating neuronal loss. At the same time an increase of DCX-positive neuronal progenitor cells outside the granular layer is observed. Additionally microglia numbers and soma sizes increase, representing an increased microgliosis. Administration of WT platelet homogenate did not lead to any structural changes compared to the saline-treated control. Furthermore results the administration of platelet homogenate in functional deficits, as is evidenced by an increase in the number of committed errors observed in the RAWM.
Conclusions
Platelet factors derived from aged APP/PS1 mice convey structural and functional hippocampal dysfunction in healthy young mice.