Moderate and advanced Alzheimer's patients exhibit platelet activation differences.
We previously reported that platelets from advanced sporadic Alzheimer's disease (AD) patients exhibit two defects: first, an aberrant signal transduction presenting as a thrombin-induced hyperacidification, which is more severe for donors with the apolipoprotein E4 allele (apoE4), and second, an AD-specific Amyloid Precursor Protein (APP) processing defect that presents as retention of APP on the activated platelets' surface and in independent of the apo E allele. This retention of membrane APP correlates with decreased release of soluble APP. To determine at what stage in the disease progression these defects appear, we performed signal transduction and secretion studies on moderate AD patients. Thrombin-activated platelets from these patients do not exhibit either hyperacidification or APP retention; their APP processing and secretion are normal by Western blotting, suggesting that the two platelet defects appear in the advanced stages of AD.
Davies
T A
TA
Department of Biochemistry, Boston University School of Medicine, MA 02118, USA.
Long
H J
HJ
Tibbles
H E
HE
Sgro
K R
KR
Wells
J M
JM
Rathbun
W H
WH
Seetoo
K F
KF
McMenamin
M E
ME
Smith
S J
SJ
Feldman
R G
RG
Levesque
C A
CA
Fine
R E
RE
Simons
E R
ER
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D016564:Amyloid beta-Protein Precursor / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D018450:Disease Progression; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D007202:Indicators and Reagents; D019007:P-Selectin; D013917:Thrombin; D002118:Calcium