Novel plasma biomarker surrogating cerebral amyloid deposition |
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Authors: | 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 |
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Institution: | *1Koichi Tanaka Laboratory of Advanced Science and Technology, Shimadzu Corporation, Kyoto, Japan.;*2Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.;*3Hospital, National Center for Geriatrics and Gerontology, Obu, Japan.;*4BioBank, National Center for Geriatrics and Gerontology, Obu, Japan. |
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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. |
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Keywords: | Alzheimer’ s disease amyloid β -protein biomarker mass spectrometry immunoprecipitation PiB amyloid imaging |
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