title: Abnormal platelet amyloid-β protein precursor (AβPP) metabolism in Alzheimer's disease: identification and characterization of a new AβPP isoform as potential biomarker.
abstract: Previous findings demonstrated an altered pattern of amyloid-β protein precursor (AβPP) expression in platelets of Alzheimer's disease (AD) patients compared with either healthy control subjects or patients with non-Alzheimer-type dementia. In an attempt to explore the diagnostic potential of platelet AβPP metabolism, we have generated monoclonal antibodies directed to the N-terminal part of AβPP. We have observed two different antibody recognition patterns of AβPP: one resembling previously described 130 kDa and 105 kDa species and a novel AβPP 115 kDa form. This form was significantly increased in platelets of the mild cognitive impairment and AD group as compared to control subjects. The abundance of AβPP 115 kDa species correlated with the previously described AβPP 130/105 kDa ratio as well as with Mini-Mental State Examination score. Despite the inability of these particular monoclonal antibodies to recognize native forms of AβPP, identification of a new AβPP isoform in platelets as a potential AD biomarker can provide an additional tool for the development of a reliable diagnostic test to detect preclinical stages of AD.
authors: Alzheimer Disease Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden.
authors: Vesna
authors: V
authors: Jelic
authors: Göran
authors: G
authors: Hagman
authors: Natsuko Goto
authors: NG
authors: Yamamoto
authors: Yasuhiro
authors: Y
authors: Teranishi
authors: Takeshi
authors: T
authors: Nishimura
authors: Bengt
authors: B
authors: Winblad
authors: Pavel F
authors: PF
authors: Pavlov
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000097:blood* / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000097:blood*; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D060825:Cognitive Dysfunction / Q000235:genetics / Q000523:psychology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D047468:Immunoprecipitation; D007536:Isomerism; D008297:Male; D051379:Mice; D009483:Neuropsychological Tests; D015539:Platelet Activation; D012015:Reference Standards
chemical_list: D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D053327:Apolipoprotein E4; D015415:Biomarkers; D053829:Amyloid Precursor Protein Secretases