Non-age related differences in thrombin responses by platelets from male patients with advanced Alzheimer's disease.
Alzheimer's Disease(AD), characterized by a deposition of beta-amyloid peptide (beta/A4) in the brain and in the cerebral microvasculature of affected individuals, is derived from its precursor protein (beta APP) via proteolytic processing by enzyme(s) which have not yet been characterized or localized. Since platelets carry APP in one of their granules, they have been implicated as a source of the beta/A4 deposits in the microvasculature of AD patients, attributable to either an abnormality in the platelets' stimulus response, in the quantity or nature of the APP they release upon activation and/or in the processing of that protein. We show here that platelets from patients with severe AD have abnormal stimulus responses to alpha-thrombin. Specifically, these cells hyperacidify. While it is not clear why this abnormality occurs, it may contribute to aberrant granule secretion since we have demonstrated earlier that release of platelet granule contents is partially controlled by the cytoplasmic pH.
Davies
T A
TA
Department of Biochemistry, Boston University School of Medicine, MA 02118.
Fine
R E
RE
Johnson
R J
RJ
Levesque
C A
CA
Rathbun
W H
WH
Seetoo
K F
KF
Smith
S J
SJ
Strohmeier
G
G
Volicer
L
L
Delva
L
L
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D012016:Reference Values; D013917:Thrombin / Q000494:pharmacology*
D005966:Glucuronidase; D013917:Thrombin