title: Effects of oxidative stress on amyloid precursor protein processing in rat and human platelets.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative illness affecting the elderly and is characterized by beta-amyloid (Aβ) deposition in the brain (plaques) and in microvessels (Aβ-angiopathy). The reasons for Aβ deposition are not clear, but an impaired clearance of Aβ at the blood-brain barrier may be implicated and oxidative stress possibly plays a major role in this process. Platelets are of particular interest, because they contain high levels of the amyloid precursor protein (APP) and in AD an abnormal expression of platelets APP fragments was found. The aim of the present study was to investigate (1) if oxidative stress induced by hydrogen peroxide (H(2)O(2)) affects APP expression in rat and human platelets and (2) to compare the APP changes with platelets of AD patients. In rat platelets, all three fragments of APP (130-110-106 kilo Dalton, kDa) were found. H(2)O(2) (10 mM, 20 minutes) significantly reduced all three fragments in rat platelets, did not affect CD62P-staining and slightly increased the size of actin as seen in the Western blot. The effect was not seen at 1 mM H(2)O(2) and was counteracted by glutathione. Immunohistochemistry for CD62P, CD61, APP and Annexin-V was used to verify the changes at the cellular level. In platelets of young volunteers (age = 33 ± 4 years), 10 mM H(2)O(2) markedly reduced the smaller APP 110 and 106 kDa fragments after 20 minutes. Our data show that platelets of AD patients (age = 80 ± 1 years) had a significant reduced 130 kDa fragment compared to controls (age = 70 ± 2 years). In summary, oxidative stress may account for a dysfunctional processing of APP in rat and human control platelets and possibly in AD patients.
authors.affiliation: Laboratory of Psychiatry and Exp. Alzheimers Research, Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ehrlich
authors.forename: Tanja
authors.initials: T
authors.lastname: Hochstrasser
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D012701:Serotonin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D012701:Serotonin; D006861:Hydrogen Peroxide; D020778:Matrix Metalloproteinase 2