Physiology and function of platelets from patients with Alzheimer's disease.
The discovery that intact Alzheimer amyloid precursor protein is present in platelet granules, has created a great interest in the biochemistry, physiology and function of platelets of patients with Alzheimer disease (AD). In this study we monitored various biochemical and physiological parameters, such as serotonin and adenine nucleotide levels, membrane fluidity, agonist-mediated release of arachidonic acid, thromboxane formation, calcium mobilization, as well as irreversible aggregation and secretion of granule contents. Platelets of patients with AD responded poorly when stirred with weak or potent agonists on a platelet aggregometer. Although capable of agonist-mediated calcium mobilization and synthesis of thromboxanes, the aggregation response of platelets of patients with AD to thrombin and archidonate was considerably compromised. In view of the normal biochemistry and signal transduction capabilities, the compromised response of these cells to potent agonists like thrombin suggested an extrinsic defect. The present study has shown that a plasmatic factor is at least in part responsible for the functional abnormalities of AD platelets.
Rao
G H
GH
University of Minnesota Medical School, Minneapolis 55455, USA.
Peller
J D
JD
Knopman
D S
DS
White
J G
JG
D000227:Adenine Nucleotides / Q000097:blood; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000097:blood; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests; D012701:Serotonin / Q000097:blood; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology
D000227:Adenine Nucleotides; D016718:Arachidonic Acid; D002118:Calcium; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013917:Thrombin