Release of beta-amyloid from high-density platelets: implications for Alzheimer's disease pathology.
The main component of Alzheimer's disease (AD) senile plaques in the brain is amyloid-beta peptide (Abeta), a proteolytic fragment of the amyloid precursor protein (APP). Platelets contain both APP and Abeta and much evidence suggests that these cells may represent a useful tool to study both amyloidogenic and nonamyloidogenic pathways of APP processing. It has been demonstrated that platelets activated by physiological agonists, such as thrombin and collagen, specifically secrete Abeta ending at residue 40. To verify whether APP beta-processing could be observed also in an in vitro system of highly concentrated platelets, we measured the Abeta released in the incubation media of 5 x 10(9) platelets/mL by enzyme-linked immunosorbent assay (ELISA). The activation status of platelets was investigated by ultrastructural analysis. We found that Abeta(40) levels were significantly higher in incubation media of 5 x 10(9)/mL platelets in comparison with 10(8)/mL platelets (normalized values), while Abeta(42) levels were not affected by cell density. The ultrastructural analysis showed platelets at different phases of activation: some platelets were at earlier stage, characterized by granule swelling and dilution, others had granules concentrated in a compact mass in the cell centers within constricted rings of circumferential microtubules (later stage). Normally concentrated cells had the characteristic morphology of resting platelets. Our data suggest that high-density platelets undergo activation likely by increased frequency of platelet-platelet collisions. This, in turn, determines the activation of APP beta-processing with consequent release of Abeta(40). Investigating the biochemical pathways triggering Abeta secretion in platelets might provide important information for developing tools to modulate this phenomenon in AD brains.
Casoli
Tiziana
T
Neurobiology of Aging Laboratory, INRCA Research Department, Via Birarelli 8, 60121 Ancona, Italy. t.casoli@inrca.it
Di Stefano
Giuseppina
G
Giorgetti
Belinda
B
Grossi
Yessica
Y
Balietti
Marta
M
Fattoretti
Patrizia
P
Bertoni-Freddari
Carlo
C
D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D002624:Chemistry, Clinical / Q000379:methods / Q000592:standards; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D015539:Platelet Activation
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)