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

Journal of Korean Medical Science 2020³â 35±Ç 44È£ p.361 ~ 361
ÀÌÁ¾¹Î, ÀåÇý¹Î, °­½ÂÈÆ, ±èÀçÈ£, ±èÁö¼±, ±èÁØÇ¥, ±èÈñÁø, ¼­»ó¿ø, Na Duk-L.,
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ÀÌÁ¾¹Î ( Lee Jong-Min ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
ÀåÇý¹Î ( Jang Hye-Min ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
°­½ÂÈÆ ( Kang Sung-Hoon ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
±èÀçÈ£ ( Kim Jae-Ho ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
±èÁö¼± ( Kim Ji-Sun ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
±èÁØÇ¥ ( Kim Jun-Pyo ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
±èÈñÁø ( Kim Hee-Jin ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
¼­»ó¿ø ( 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 A¥â42, 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/A¥â42 (0.994) followed by p-tau/A¥â42 (0.963), A¥â42 (0.960), t-tau (0.918), and p-tau (0.684). The concordance rate between CSF A¥â42 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.

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

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