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.

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.

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.

Neutron yields from 435 MeV/nucleon Nb stopping in Nb and 272 MeV/nucleon Nb stopping in Nb and Al.

Neutron fluences were measured from 435 MeV/nucleon Nb ions stopping in a Nb target and 272 MeV/nucleon Nb ions stopping in targets of Nb and Al for neutrons above 20 MeV and at laboratory angles between 3 degrees and 80 degrees. The resultant spectra were integrated over angles to produce neutron energy distributions and over energy to produce neutron angular distributions. The total neutron yields for each system were obtained by integrating over the angular distributions. The angular distributions from all three systems are peaked forward, and the energy distributions from all three systems show an appreciable yield of neutrons with velocities greater than the beam velocity. Comparison of the total neutron yields from the two Nb + Nb systems suggests that the average neutron multiplicity decreases with decreasing projectile energy. Comparison of the total yields from the two 272 MeV/nucleon systems suggests that the total yields show the same dependence on projectile and target mass number as do total inclusive neutron cross sections. The data are compared with Boltzmann-Uehling-Uhlenbeck model calculations.