title: 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).
  
  
  CONCLUSIONS
  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: Department of Internal Medicine, Vrinnevi Hospital, Norrköping, Sweden. petter.jaremo@beta.telenordia.se
authors: Petter
authors: P
authors: Järemo
authors: Micha
authors: M
authors: Milovanovic
authors: Caroline
authors: C
authors: Buller
authors: Staffan
authors: S
authors: Nilsson
authors: Bengt
authors: B
authors: Winblad
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D010446:Peptide Fragments; C082835:thrombin receptor peptide (42-47)