Analysis of Cerebrospinal Fluid and [¹¹C]PIB PET Biomarkers for Alzheimer’s Disease with Updated Protocols

Article type: Research Article

Authors: Wang, Min Jeong^a | Yi, SangHak^a | Han, Jee-young^a | Park, So Young^b | Jang, Jae-Won^c | Chun, In Kook^d | Giau, Vo Van^e | Bagyinszky, Eva^e | Lim, Kun Taek^f | Kang, Sung Min^f | An, Seong Soo A.^e | Park, Young Ho^a | Youn, Young Chul^g | Kim, SangYun^{a; *}

Affiliations: [a] Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Republic of Korea | [b] Department of Neurology, Seoul National University College of Medicine, Seoul, Republic of Korea | [c] Department of Neurology, Kangwon National University Hospital, Chuncheon-si, Republic of Korea | [d] Department of Nuclear Medicine, School of Medicine, Kangwon National University, Chuncheon-si, Gangwon-do, Republic of Korea | [e] Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Republic of Korea | [f] People Bio, Inc., Seoul, Republic of Korea | [g] Department of Neurology, Chung-Ang University Hospital, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: SangYun Kim, MD, PhD, Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea. Tel.: +82 31 787 7462; Fax: +82 31 787 4059; E-mail: neuroksy@snu.ac.kr.

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.

Keywords: Alzheimer’s disease, biomarker, cerebrospinal fluid, diagnosis, Pittsburgh compound B, protocol

DOI: 10.3233/JAD-160143

Journal: Journal of Alzheimer's Disease, vol. 52, no. 4, pp. 1403-1413, 2016