Abnormal Platelet Amyloid-β Protein Precursor (AβPP) Metabolism in Alzheimer's Disease: Identification and Characterization of a New AβPP Isoform as Potential Biomarker

Article type: Research Article

Authors: Jelic, Vesna^a | Hagman, Göran^a | Yamamoto, Natsuko Goto^b | Teranishi, Yasuhiro^b | Nishimura, Takeshi^c | Winblad, Bengt^a | Pavlov, Pavel F.^{a; *}

Affiliations: [a] Alzheimer Disease Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden | [b] Dainippon Sumitomo Pharma Co., Ltd., Pharmacology Research Laboratories, Discovery Pharmacology I, Suita, Osaka, Japan | [c] Dainippon Sumitomo Pharma Co., Ltd., Development Management, Group I, Chuo-ku, Osaka, Japan

Correspondence: [*] Correspondence to: Pavel F. Pavlov, Alzheimer Disease Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Novum floor 5, SE-141 57 Huddinge, Sweden. Tel.: +46 858583629; E-mail: [email protected].

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.

Keywords: Alzheimer's disease, amyloid-β protein precursor, biomarker, platelets

DOI: 10.3233/JAD-122122

Journal: Journal of Alzheimer's Disease, vol. 35, no. 2, pp. 285-295, 2013