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.
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.
Authors: Kristine S Alexander; Neil A Zakai; Sarah Gillett; Leslie A McClure; Virginia Wadley; Fred Unverzagt; Mary Cushman Journal: Neurology Date: 2014-09-10 Impact factor: 9.910
Authors: Senthil K Vasan; Klaus Rostgaard; Henrik Ullum; Mads Melbye; Henrik Hjalgrim; Gustaf Edgren Journal: PLoS One Date: 2015-06-04 Impact factor: 3.240
Authors: Benedetta Izzi; Alfonsina Tirozzi; Chiara Cerletti; Maria Benedetta Donati; Giovanni de Gaetano; Marc F Hoylaerts; Licia Iacoviello; Alessandro Gialluisi Journal: Int J Mol Sci Date: 2020-11-21 Impact factor: 5.923