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Principal Investigator  
Principal Investigator's Name: DANIEL CAPON
Proposed Analysis: My laboratory research is focused on creating novel biomolecules for human diagnostic and therapeutic applications. I have invented a number of widely adopted technologies that include Fc fusion proteins (at Genentech), Chimeric Antigen Receptors, or CAR (at Cell Genesys), fully human antibodies in mice (at Abgenix/Amgen), and viral vectors for HIV phenotypic drug resistance/susceptibility diagnostic testing (at Monogram Biosciences/Labcorp). Currently my lab is developing a novel plasma biomarker/phenotyping system using a method I invented that employs cooperative, flexible antibodies with non-peptide hinges to pre-concentrate amyloid beta from the blood allowing for its direct analysis by mass spectrometry [D. Capon et al (2011) “Flexible Antibodies with Non-peptide Hinges”, Proc. Jpn. Acad., Ser. B, Vol. 87, 603-616; D. Capon (2014) "Affinity Support and Method for Trapping Substance Using The Same", Intl. Pat. Application No. WO 2014/014563; N. Kaneko, A. Yoshimori, Y. Yamamoto, D. Capon, T. Shimada, T. Sato and K. Tanaka (2013) "Multi epitope-targeting immunoprecipitation using F(ab') fragments with high affinity and specificity for the enhanced detection of a peptide with MALDI-TOF MS", Anal. Chem. 2013, 85, 3152−3159]. To date, my method has been reported by the National Center for Geriatrics and Gerontology (NCGG) in Japan, in collaboration with Shimadzu Corporation, to detect a change in the ratio of a novel N-Terminally Extended (NTE) Abeta peptide (APP669-711) relative to the classic Abeta1-42 peptide. This ratio acts as a surrogates of PiB amyloid brain imaging by PET (N. Kaneko, A. Nakamura, Y. Washimi, T. Kato, T. Sakurai,Y. Arahata, M. Bundo, A. Takeda, S. Niida, K. Ito, K. Toba, K. Tanaka and K. Yanagisawa (2014) “Novel plasma biomarker surrogating cerebral amyloid deposition”, Proc. Jpn. Acad., Ser. B, Vol. 90, 653-664]. APP669-711 is a 43 amino acid peptide extending from position -3 (three amino acids upstream of the beta secretase cleavage site) to position +40. I would like to analyze the ADNI database to identify plasma samples available in the ADNI biomarker repository that can be used to replicate the aforementioned biomarker studies carried out at the NCGG and Shimadzu. Since PiB was employed in all of the reported PET scans carried out at the NCGG, it will be equally important to determine whether there are differences in the biomarker between patients that have been imaged using PiB vs. other agents for amyloid imaging such as Florbetapir now more commonly used in the United States and Canada.
Additional Investigators