P-selectin paradox and dementia of the Alzheimer type: Circulating P-selectin is increased but platelet-bound P-selectin after agonist provocation is compromised

Abstract

Objective. Knowledge concerning the neurobiological importance of platelets in Alzheimer's disease (AD) is sparse. P-selectin, which is located together with β-amyloid precursor proteins in platelet α-granules, is also found in endothelial cells. Upon activation, P-selectin is relocated to cell surfaces where it acts as a receptor. Subsequently, the protein is cleaved from the membrane, to then be circulated. We investigated P-selectin behavior in AD dementia. Methods. We recruited 23 persons diagnosed moderate AD and 17 healthy elders without obvious memory problems. Circulating P-selectin was analyzed using an ELISA technique and flow cytometry was used to measure surface-bound P-selectin. The latter measure was carried out without provocation (platelet activity) and after in vitro agonist stimulation (platelet reactivity). A thrombin-receptor activating peptide (TRAP-6) (74 μmol/L)) was used as a platelet agonist. Results. Soluble P-selectin was augmented in AD (p = 0.019) but platelet membrane-attached P-selectin did not differ from controls. AD diagnosis was associated with less surface-bound P-selectin after provocation. Significant results were obtained when 74 μmol/L TRAP-6 was used as a platelet agonist (p = 0.0008). Conclusion. This study describes apparently paradoxical P-selectin reactions in moderate AD. While soluble P-selectin was higher in the disease group, membrane-attached P-selectin without agonist stimulation was no different between the disease and control groups. In contrast, AD was linked to lower platelet reactivity. The current findings encourage further research into this P-selectin paradox and its relevance for AD and, perhaps, other types of dementia as well.

Key Words::

• Alzheimer's disease
• endothelium
• platelet activity
• platelet reactivity
• P-selectin

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

We are grateful for grants from the Swedish Board for Health and Welfare and Pfizer AB, Sweden. The authors acknowledge financial support from the Ahlen's Foundation and the Gun and Bertil Stohne´s Foundation. The Magn. Bergvall´s Foundation, the ‘Stiftelsen för Gamla Tjänarinnor’ and the Swedish Alzheimer Foundation also contributed to the research.