Comparison of Two Analytical Platforms in Cerebrospinal Fluid Biomarkers for the Classification of Alzheimer’s Disease Spectrum with Amyloid PET Imaging

Article type: Research Article

Authors: Lim, Ho Jae^{a; 1} | Park, Jung Eun^{a; b; 1} | Kim, Byeong C.^{c; *} | Choi, Seong-Min^c | Song, Min-Kyung^c | Cho, Soo Hyun^c | Seo, Hyeon Jeong^c | Kim, Jahae^d | Song, Ho-Chun^d | Choi, Kyu Yeong^e | Lee, Jang Jae^e | Kim, Hoo-Won^f | Ha, Jung-Min^g | Song, Woo Keun^h | Park, Sung-Gyoo^h | Lee, Jung Sup^{a; b} | Lee, Kun Ho^{a; e; i; *}

Affiliations: [a] Department of Biomedical Science, Chosun University, Gwangju, Republic of Korea | [b] BK21-plus Research Team for Bioactive Control Technology, Chosun University, Gwangju, Republic of Korea | [c] Department of Neurology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea | [d] Department of Nuclear Medicine, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea | [e] Gwangju Alzheimer’s Disease and Related Dementias Cohort Center, Chosun University, Gwangju, Republic of Korea | [f] Department of Neurology, Chosun University School of Medicine, Gwangju, Republic of Korea | [g] Department of Nuclear Medicine, Chosun University School of Medicine, Gwangju, Republic of Korea | [h] Department of Life Science, Bioimaging and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea | [i] Department of Neural Development and Disease, Korea Brain Research Institute, Daegu, Republic of Korea

Correspondence: [*] Correspondence to: Byeong C. Kim, MD, PhD, Department of Neurology, Chonnam National University Medical School & Hospital, 42 Jebongro, Dongku, Gwangju 61469, Republic of Korea. Tel.: +82 62 220 6123; E-mail: [email protected]. and Kun Ho Lee, PhD, Department of Biomedical Science, Chosun University, 309 Pilmundaero, Dongku, Gwangju 61452, Republic of Korea. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ1-42), total tau protein (t-Tau), and phosphorylated Tau (p-Tau) are ATN biomarkers for Alzheimer’s disease (AD) and reflect pathogenic changes in the brain. CSF biomarkers of AD are considered for inclusion in the diagnostic criteria for research and clinical purposes to reduce the uncertainty of clinical diagnosis and to distinguish among AD stages. Objective:This study aims to compare two commercially available analytical platforms with respect to accuracy and the potential for early diagnosis of AD. Methods:A total of 211 CSF samples from healthy control (HC) and AD subjects were analyzed using two analytical platforms, INNOTEST ELISA and INNOBIA AlzBio3 xMAP kits. The accuracy of diagnosis and AUC values distinguishing study groups were compared between the two analytical platforms. Results:The absolute values for Aβ1-42, t-Tau, and p-Tau181 levels differed between the two platforms. The Aβ1-42 levels decreased, while t-Tau and p-Tau levels increased according to the AD stages. The AUC of Aβ1-42 and t-Tau, which distinguish the early stages of AD (preclinical and prodromal AD), were similar between the two platforms, whereas there were significant differences in p-Tau AUC values. CSF p-Tau using the INNOBIA was highly accurate for distinguishing both preclinical AD (AUC = 0.826, cut-off score≥38.89) and prodromal AD (AUC = 0.862, cut-off score≥41.88) from HC. Conclusion:The accuracy of CSF p-Tau levels in the preclinical and prodromal AD is higher for the INNOBIA than the INNOTEST, and the early stage AD can be accurately distinguished from HC.

Keywords: Alzheimer’s disease, biomarkers, cerebrospinal fluid, immunoassay, preclinical AD, tau protein

DOI: 10.3233/JAD-191331

Journal: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 949-958, 2020