Min Jeong Wang1, SangHak Yi1, Jee-Young Han1, So Young Park2, Jae-Won Jang3, In Kook Chun4, Vo Van Giau5, Eva Bagyinszky5, Kun Taek Lim6, Sung Min Kang6, Seong Soo A An5, Young Ho Park1, Young Chul Youn7, SangYun Kim1. 1. Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Republic of Korea. 2. Department of Neurology, Seoul National University College of Medicine, Seoul, Republic of Korea. 3. Department of Neurology, Kangwon National University Hospital, Chuncheon-si, Republic of Korea. 4. Department of Nuclear Medicine, School of Medicine, Kangwon National University, Chuncheon-si, Gangwon-do, Republic of Korea. 5. Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Republic of Korea. 6. People Bio, Inc., Seoul, Republic of Korea. 7. Department of Neurology, Chung-Ang University Hospital, Seoul, Republic of Korea.
Abstract
BACKGROUND: Recently, a Korean research group suggested a consensus protocol, based on the Alzheimer's Disease Neuroimaging Initiative study protocol but with modifications for minimizing the confounding factors, for the evaluation of cerebrospinal fluid (CSF) biomarkers. OBJECTIVE: Here, we analyzed fluid and imaging biomarkers of Alzheimer's disease (AD) in Korean population. We used the updated protocol to propose a more accurate CSF biomarker value for the diagnosis of AD. METHODS: Twenty-seven patients with AD and 30 cognitively normal controls (NC) were enrolled. CSF was collected from 55 subjects (patients with AD = 26, NC = 29) following the Korea consensus protocol. CSF biomarkers were measured using the INNO-BIA AlzBio3 immunoassay, and Pittsburgh compound B (PIB) positron emission tomography (PET) scans were also performed. RESULTS: The cutoff values of CSF amyloid beta 1-42 (Aβ42), total tau (t-Tau), and phosphorylated tau (p-Tau) proteins were 357.1 pg/ml, 83.35 pg/ml, and 38.00 pg/ml, respectively. The cutoff values of CSF t-Tau/Aβ42 and p-Tau/Aβ42 ratio- were 0.210 (sensitivity 100%, specificity 86.21%) and 0.1350 (sensitivity 88.46%, specificity of 92.86%). The concordance rate with PIB-PET was higher using the CSF t-Tau/Aβ42 ratio (κ= 0.849, CI 0.71-0.99) than CSF Aβ42 alone (κ= 0.703, CI 0.51-0.89). CONCLUSIONS: Here, we improved controversial factors associated with the previous CSF study protocol and suggested a new cutoff value for the diagnosis of AD. Our results showed good diagnostic performance for differentiation of AD. Thus, we expect our findings could be a cornerstone in the establishment and clinical application of biomarkers for AD diagnosis.
BACKGROUND: Recently, a Korean research group suggested a consensus protocol, based on the Alzheimer's Disease Neuroimaging Initiative study protocol but with modifications for minimizing the confounding factors, for the evaluation of cerebrospinal fluid (CSF) biomarkers. OBJECTIVE: Here, we analyzed fluid and imaging biomarkers of Alzheimer's disease (AD) in Korean population. We used the updated protocol to propose a more accurate CSF biomarker value for the diagnosis of AD. METHODS: Twenty-seven patients with AD and 30 cognitively normal controls (NC) were enrolled. CSF was collected from 55 subjects (patients with AD = 26, NC = 29) following the Korea consensus protocol. CSF biomarkers were measured using the INNO-BIA AlzBio3 immunoassay, and Pittsburgh compound B (PIB) positron emission tomography (PET) scans were also performed. RESULTS: The cutoff values of CSF amyloid beta 1-42 (Aβ42), total tau (t-Tau), and phosphorylated tau (p-Tau) proteins were 357.1 pg/ml, 83.35 pg/ml, and 38.00 pg/ml, respectively. The cutoff values of CSF t-Tau/Aβ42 and p-Tau/Aβ42 ratio- were 0.210 (sensitivity 100%, specificity 86.21%) and 0.1350 (sensitivity 88.46%, specificity of 92.86%). The concordance rate with PIB-PET was higher using the CSF t-Tau/Aβ42 ratio (κ= 0.849, CI 0.71-0.99) than CSF Aβ42 alone (κ= 0.703, CI 0.51-0.89). CONCLUSIONS: Here, we improved controversial factors associated with the previous CSF study protocol and suggested a new cutoff value for the diagnosis of AD. Our results showed good diagnostic performance for differentiation of AD. Thus, we expect our findings could be a cornerstone in the establishment and clinical application of biomarkers for AD diagnosis.
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Authors: Min Jeong Wang; SangHak Yi; Jee-Young Han; So Young Park; Jae-Won Jang; In Kook Chun; Sang Eun Kim; Byoung Sub Lee; Gwang Je Kim; Ji Sun Yu; Kuntaek Lim; Sung Min Kang; Young Ho Park; Young Chul Youn; Seong Soo A An; SangYun Kim Journal: Alzheimers Res Ther Date: 2017-12-15 Impact factor: 6.982
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