P-selectin paradox and dementia of the Alzheimer type: Circulating P-selectin is increased but platelet-bound P-selectin after agonist provocation is compromised
2013 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, Vol. 73, no 2, 170-174 p.Article in journal (Refereed) Published
Objective. Knowledge concerning the neurobiological importance of platelets in Alzheimers disease (AD) is sparse. P-selectin, which is located together with beta-amyloid precursor proteins in platelet alpha-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 mu mol/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 mu mol/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.
Place, publisher, year, edition, pages
Informa Healthcare, 2013. Vol. 73, no 2, 170-174 p.
Alzheimers disease, endothelium, platelet activity, platelet reactivity, P-selectin
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-90754DOI: 10.3109/00365513.2013.764572ISI: 000315896000012PubMedID: 23421771OAI: oai:DiVA.org:liu-90754DiVA: diva2:614698
Funding Agencies|Swedish Board for Health and Welfare||Pfizer AB, Sweden||Ahlens Foundation||Gun and Bertil Stohnes Foundation||2013-04-052013-04-052013-04-16