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Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum

Journal of Korean Medical Science 2020년 35권 44호 p.361 ~ 361
Lee Jong-Min, 장혜민, 강승훈, 김재호, 김지선, 김준표, 김희진, 서상원, Na Duk-L.,
소속 상세정보
 ( Lee Jong-Min ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
장혜민 ( Jang Hye-Min ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
강승훈 ( Kang Sung-Hoon ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
김재호 ( Kim Jae-Ho ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
김지선 ( Kim Ji-Sun ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
김준표 ( Kim Jun-Pyo ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
김희진 ( Kim Hee-Jin ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
서상원 ( Seo Sang-Won ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
 ( Na Duk-L. ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology

Abstract


Background: Cerebrospinal fluid (CSF) biomarkers are increasingly used in clinical practice for the diagnosis of Alzheimer's disease (AD). We aimed to 1) determine cutoff values of CSF biomarkers for AD, 2) investigate their clinical utility by estimating a concordance with amyloid positron emission tomography (PET), and 3) apply ATN (amyloid/tau/neurodegeneration) classification based on CSF results.

Methods: We performed CSF analysis in 51 normal controls (NC), 23 mild cognitive impairment (MCI) and 65 AD dementia (ADD) patients at the Samsung Medical Center in Korea. We attempted to develop cutoff of CSF biomarkers for differentiating ADD from NC using receiver operating characteristic analysis. We also investigated a concordance between CSF and amyloid PET results and applied ATN classification scheme based on CSF biomarker abnormalities to characterize our participants.

Results: CSF Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) significantly differed across the three groups. The area under curve for the differentiation between NC and ADD was highest in t-tau/Aβ42 (0.994) followed by p-tau/Aβ42 (0.963), Aβ42 (0.960), t-tau (0.918), and p-tau (0.684). The concordance rate between CSF Aβ42 and amyloid PET results was 92%. Finally, ATN classification based on CSF biomarker abnormalities led to a majority of NC categorized into A-T-N-(73%), MCI as A+T-N-(30%)/A+T+N+(26%), and ADD as A+T+N+(57%).

Conclusion: CSF biomarkers had high sensitivity and specificity in differentiating ADD from NC and were as accurate as amyloid PET. The ATN subtypes based on CSF biomarkers may further serve to predict the prognosis.

키워드

Alzheimer Disease; Cerebrospinal Fluid; Amyloid; tau; Positron Emission Tomography; Biomarkers; Classification

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