Novel plasma biomarker surrogating cerebral amyloid deposition

Naoki KANEKO; Akinori NAKAMURA; Yukihiko WASHIMI; Takashi KATO; Takashi SAKURAI; Yutaka ARAHATA; Masahiko BUNDO; Akinori TAKEDA; Shumpei NIIDA; Kengo ITO; Kenji TOBA; Koichi TANAKA; Katsuhiko YANAGISAWA

doi:10.2183/pjab.90.353

Original Articles

Novel plasma biomarker surrogating cerebral amyloid deposition

Naoki KANEKO, Akinori NAKAMURA, Yukihiko WASHIMI, Takashi KATO, Takashi SAKURAI, Yutaka ARAHATA, Masahiko BUNDO, Akinori TAKEDA, Shumpei NIIDA, Kengo ITO, Kenji TOBA, Koichi TANAKA, Katsuhiko YANAGISAWA

Author information

Naoki KANEKO
Koichi Tanaka Laboratory of Advanced Science and Technology, Shimadzu Corporation
Akinori NAKAMURA
Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology
Yukihiko WASHIMI
Hospital, National Center for Geriatrics and Gerontology
Takashi KATO
Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology
Hospital, National Center for Geriatrics and Gerontology
Takashi SAKURAI
Hospital, National Center for Geriatrics and Gerontology
Yutaka ARAHATA
Hospital, National Center for Geriatrics and Gerontology
Masahiko BUNDO
Hospital, National Center for Geriatrics and Gerontology
Akinori TAKEDA
Hospital, National Center for Geriatrics and Gerontology
Shumpei NIIDA
BioBank, National Center for Geriatrics and Gerontology
Kengo ITO
Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology
Hospital, National Center for Geriatrics and Gerontology
Kenji TOBA
Hospital, National Center for Geriatrics and Gerontology
Koichi TANAKA
Koichi Tanaka Laboratory of Advanced Science and Technology, Shimadzu Corporation
Katsuhiko YANAGISAWA Corresponding author
Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology

Keywords: Alzheimer’s disease, amyloid β-protein, biomarker, mass spectrometry, immunoprecipitation, PiB amyloid imaging

JOURNAL FREE ACCESS FULL-TEXT HTML

2014 Volume 90 Issue 9 Pages 353-364

DOI https://doi.org/10.2183/pjab.90.353

Details

Abstract

Alzheimer’s disease (AD) is the most common and devastating dementia. Simple and practical biomarkers for AD are urgently required for accurate diagnosis and to facilitate the development of disease-modifying interventions. The subjects for the study were selected on the basis of PiB amyloid imaging by PET. Forty PiB-positive (PiB+) individuals, including cognitively healthy controls (HC), and mild cognitive impairment and AD individuals, and 22 PiB-negative (PiB−) HC participated. Employing our novel highly sensitive immunoprecipitation-mass spectrometry, we measured plasma amyloid β-proteins (Aβs; Aβ1-40 and Aβ1-42) and Aβ-approximate peptides (AβAPs), which were cleaved from amyloid precursor protein (APP). Among the AβAPs, APP669-711 appeared to be a good reference for deciphering pathological change of Aβ1-42. We evaluated the performance of the ratio of APP669-711 to Aβ1-42 (APP669-711/Aβ1-42) as a biomarker. APP669-711/Aβ1-42 significantly increased in the PiB+ groups. The sensitivity and specificity to discriminate PiB+ individuals from PiB− individuals were 0.925 and 0.955, respectively. Our plasma biomarker precisely surrogates cerebral amyloid deposition.

Corresponding author

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