Cargando…

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

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 emi...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Jongmin, Jang, Hyemin, Kang, Sung Hoon, Kim, Jaeho, Kim, Ji Sun, Kim, Jun Pyo, Kim, Hee Jin, Seo, Sang Won, Na, Duk L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Medical Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669457/
https://www.ncbi.nlm.nih.gov/pubmed/33200589
http://dx.doi.org/10.3346/jkms.2020.35.e361
_version_ 1783610575190753280
author Lee, Jongmin
Jang, Hyemin
Kang, Sung Hoon
Kim, Jaeho
Kim, Ji Sun
Kim, Jun Pyo
Kim, Hee Jin
Seo, Sang Won
Na, Duk L.
author_facet Lee, Jongmin
Jang, Hyemin
Kang, Sung Hoon
Kim, Jaeho
Kim, Ji Sun
Kim, Jun Pyo
Kim, Hee Jin
Seo, Sang Won
Na, Duk L.
author_sort Lee, Jongmin
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7669457
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Korean Academy of Medical Sciences
record_format MEDLINE/PubMed
spelling pubmed-76694572020-11-19 Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum Lee, Jongmin Jang, Hyemin Kang, Sung Hoon Kim, Jaeho Kim, Ji Sun Kim, Jun Pyo Kim, Hee Jin Seo, Sang Won Na, Duk L. J Korean Med Sci Original Article 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. The Korean Academy of Medical Sciences 2020-10-06 /pmc/articles/PMC7669457/ /pubmed/33200589 http://dx.doi.org/10.3346/jkms.2020.35.e361 Text en © 2020 The Korean Academy of Medical Sciences. https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lee, Jongmin
Jang, Hyemin
Kang, Sung Hoon
Kim, Jaeho
Kim, Ji Sun
Kim, Jun Pyo
Kim, Hee Jin
Seo, Sang Won
Na, Duk L.
Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum
title Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum
title_full Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum
title_fullStr Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum
title_full_unstemmed Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum
title_short Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum
title_sort cerebrospinal fluid biomarkers for the diagnosis and classification of alzheimer's disease spectrum
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669457/
https://www.ncbi.nlm.nih.gov/pubmed/33200589
http://dx.doi.org/10.3346/jkms.2020.35.e361
work_keys_str_mv AT leejongmin cerebrospinalfluidbiomarkersforthediagnosisandclassificationofalzheimersdiseasespectrum
AT janghyemin cerebrospinalfluidbiomarkersforthediagnosisandclassificationofalzheimersdiseasespectrum
AT kangsunghoon cerebrospinalfluidbiomarkersforthediagnosisandclassificationofalzheimersdiseasespectrum
AT kimjaeho cerebrospinalfluidbiomarkersforthediagnosisandclassificationofalzheimersdiseasespectrum
AT kimjisun cerebrospinalfluidbiomarkersforthediagnosisandclassificationofalzheimersdiseasespectrum
AT kimjunpyo cerebrospinalfluidbiomarkersforthediagnosisandclassificationofalzheimersdiseasespectrum
AT kimheejin cerebrospinalfluidbiomarkersforthediagnosisandclassificationofalzheimersdiseasespectrum
AT seosangwon cerebrospinalfluidbiomarkersforthediagnosisandclassificationofalzheimersdiseasespectrum
AT nadukl cerebrospinalfluidbiomarkersforthediagnosisandclassificationofalzheimersdiseasespectrum