Activated Alzheimer disease platelets retain more beta amyloid precursor protein.
Upon activation, platelet alpha-granules' soluble contents are secreted and membrane-bound contents are translocated to the plasma membrane. Membrane-bound proteins include the beta-amyloid precursor protein (APP) from which the beta-amyloid (A beta) deposits found surrounding the cerebrovasculature of patients with Alzheimer's Disease (AD) may originate. We show here that activated platelets from AD patients exhibit less APP processing, retain more of the protein on their surface, and secrete less as soluble fragments than do controls. Surface labeling demonstrated that there is little APP or CD62 on the surface of resting platelets. Upon activation, control platelets exhibited more of both proteins on their surface, while advanced AD patients exhibited similar amounts of CD62 as controls, but retained significantly more surface APP. AD platelets secreted similar amounts of most soluble alpha-granule contents as controls, but less APP fragments. Together these results suggest a processing defect that may account for greater deposition of A beta-containing products in the vasculature to which activated platelets adhere.
Davies
T A
TA
Boston University School of Medicine, MA 02118, USA.
Long
H J
HJ
Sgro
K
K
Rathbun
W H
WH
McMenamin
M E
ME
Seetoo
K
K
Tibbles
H
H
Billingslea
A M
AM
Fine
R E
RE
Fishman
J B
JB
Levesque
C A
CA
Smith
S J
SJ
Wells
J M
JM
Simons
E R
ER
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D016229:Amyloid beta-Peptides / Q000097:blood*; D016564:Amyloid beta-Protein Precursor / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D015550:Cell Degranulation; D002462:Cell Membrane / Q000378:metabolism; D003704:Dementia / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008297:Male; D015539:Platelet Activation / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor