Tags

Type your tag names separated by a space and hit enter

Concordance Between Cerebrospinal Fluid Biomarkers with Alzheimer's Disease Pathology Between Three Independent Assay Platforms.
J Alzheimers Dis. 2018; 61(1):169-183.JA

Abstract

BACKGROUND

To enhance the accuracy of clinical diagnosis for Alzheimer's disease (AD), pre-mortem biomarkers have become increasingly important for diagnosis and for participant recruitment in disease-specific treatment trials. Cerebrospinal fluid (CSF) biomarkers provide a low-cost alternative to positron emission tomography (PET) imaging for in vivo quantification of different AD pathological hallmarks in the brains of affected subjects; however, consensus around the best platform, most informative biomarker and correlations across different methodologies are controversial.

OBJECTIVE

Assessing levels of Aβ-amyloid and tau species determined using three different versions of immunoassays, the current study explored the ability of CSF biomarkers to predict PET Aβ-amyloid (32 Aβ-amyloid-and 45 Aβ-amyloid+), as well as concordance between CSF biomarker levels and PET Aβ-amyloid imaging.

METHODS

Prediction and concordance analyses were performed using a sub-cohort of 77 individuals (48 healthy controls, 15 with mild cognitive impairment, and 14 with AD) from the Australian Imaging Biomarker and Lifestyle study of aging.

RESULTS

Across all three platforms, the T-tau/Aβ42 ratio biomarker had modestly higher correlation with SUVR/BeCKeT (ρ= 0.69-0.8) as compared with Aβ42 alone (ρ= 0.66-0.75). Differences in CSF biomarker levels between the PET Aβ-amyloid-and Aβ-amyloid+ groups were strongest for the Aβ42/Aβ40 and T-tau/Aβ42 ratios (p < 0.0001); however, comparison of predictive models for PET Aβ-amyloid showed no difference between Aβ42 alone and the T-tau/Aβ42 ratio.

CONCLUSION

This study confirms strong concordance between CSF biomarkers and PET Aβ-amyloid status is independent of immunoassay platform, supporting their utility as biomarkers in clinical practice for the diagnosis of AD and for participant enrichment in clinical trials.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Doecke JD
CSIRO Health and Biosecurity/Australian e-Health Research Centre, Brisbane, QLD, Australia. Cooperative Research Centre for Mental Health, Parkville, VIC, Australia.
Rembach A
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
Villemagne VL
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia. Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia.
Varghese S
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia. National Dementia Diagnostics Laboratory, The University of Melbourne, VIC, Australia.
Rainey-Smith S
Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia.
Sarros S
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia. National Dementia Diagnostics Laboratory, The University of Melbourne, VIC, Australia.
Evered LA
Department of Anaesthesia and Perioperative Pain Medicine, Centre for Anaesthesia and Cognitive Function, St Vincent's Hospital, Melbourne, Australia.
Fowler CJ
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
Pertile KK
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
Rumble RL
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
Trounson B
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
Taddei K
Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia.
Laws SM
Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia.
Macaulay SL
CSIRO Health and Biosecurity/Australian e-Health Research Centre, Brisbane, QLD, Australia.
Bush AI
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
Ellis KA
Academic Unit for Psychiatry of Old Age, The University of Melbourne, Melbourne, Australia.
Martins R
Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia.
Ames D
Academic Unit for Psychiatry of Old Age, The University of Melbourne, Melbourne, Australia.
Silbert B
Department of Anaesthesia and Perioperative Pain Medicine, Centre for Anaesthesia and Cognitive Function, St Vincent's Hospital, Melbourne, Australia.
Vanderstichele H
ADx NeuroSciences, Gent, Belgium.
Masters CL
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia. National Dementia Diagnostics Laboratory, The University of Melbourne, VIC, Australia.
Darby DG
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
Li QX
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia. National Dementia Diagnostics Laboratory, The University of Melbourne, VIC, Australia.
Collins S
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia. Department of Medicine (RMH), The University of Melbourne, Parkville, Australia. National Dementia Diagnostics Laboratory, The University of Melbourne, VIC, Australia.
AIBL Research Group
No affiliation info available

MeSH

AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognition DisordersFemaleHumansMaleMental Status SchedulePeptide FragmentsPositron-Emission TomographyROC Curvetau Proteins

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29171991

Citation

Doecke, James D., et al. "Concordance Between Cerebrospinal Fluid Biomarkers With Alzheimer's Disease Pathology Between Three Independent Assay Platforms." Journal of Alzheimer's Disease : JAD, vol. 61, no. 1, 2018, pp. 169-183.
Doecke JD, Rembach A, Villemagne VL, et al. Concordance Between Cerebrospinal Fluid Biomarkers with Alzheimer's Disease Pathology Between Three Independent Assay Platforms. J Alzheimers Dis. 2018;61(1):169-183.
Doecke, J. D., Rembach, A., Villemagne, V. L., Varghese, S., Rainey-Smith, S., Sarros, S., Evered, L. A., Fowler, C. J., Pertile, K. K., Rumble, R. L., Trounson, B., Taddei, K., Laws, S. M., Macaulay, S. L., Bush, A. I., Ellis, K. A., Martins, R., Ames, D., Silbert, B., ... Collins, S. (2018). Concordance Between Cerebrospinal Fluid Biomarkers with Alzheimer's Disease Pathology Between Three Independent Assay Platforms. Journal of Alzheimer's Disease : JAD, 61(1), 169-183. https://doi.org/10.3233/JAD-170128
Doecke JD, et al. Concordance Between Cerebrospinal Fluid Biomarkers With Alzheimer's Disease Pathology Between Three Independent Assay Platforms. J Alzheimers Dis. 2018;61(1):169-183. PubMed PMID: 29171991.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Concordance Between Cerebrospinal Fluid Biomarkers with Alzheimer's Disease Pathology Between Three Independent Assay Platforms. AU - Doecke,James D, AU - Rembach,Alan, AU - Villemagne,Victor L, AU - Varghese,Shiji, AU - Rainey-Smith,Stephanie, AU - Sarros,Shannon, AU - Evered,Lisbeth A, AU - Fowler,Christopher J, AU - Pertile,Kelly K, AU - Rumble,Rebecca L, AU - Trounson,Brett, AU - Taddei,Kevin, AU - Laws,Simon M, AU - Macaulay,S Lance, AU - Bush,Ashley I, AU - Ellis,Kathryn A, AU - Martins,Ralph, AU - Ames,David, AU - Silbert,Brendan, AU - Vanderstichele,Hugo, AU - Masters,Colin L, AU - Darby,David G, AU - Li,Qiao-Xin, AU - Collins,Steven, AU - ,, PY - 2017/11/25/pubmed PY - 2018/7/14/medline PY - 2017/11/25/entrez KW - Amyloid KW - PET KW - biomarker KW - cerebrospinal fluid KW - concordance SP - 169 EP - 183 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 61 IS - 1 N2 - BACKGROUND: To enhance the accuracy of clinical diagnosis for Alzheimer's disease (AD), pre-mortem biomarkers have become increasingly important for diagnosis and for participant recruitment in disease-specific treatment trials. Cerebrospinal fluid (CSF) biomarkers provide a low-cost alternative to positron emission tomography (PET) imaging for in vivo quantification of different AD pathological hallmarks in the brains of affected subjects; however, consensus around the best platform, most informative biomarker and correlations across different methodologies are controversial. OBJECTIVE: Assessing levels of Aβ-amyloid and tau species determined using three different versions of immunoassays, the current study explored the ability of CSF biomarkers to predict PET Aβ-amyloid (32 Aβ-amyloid-and 45 Aβ-amyloid+), as well as concordance between CSF biomarker levels and PET Aβ-amyloid imaging. METHODS: Prediction and concordance analyses were performed using a sub-cohort of 77 individuals (48 healthy controls, 15 with mild cognitive impairment, and 14 with AD) from the Australian Imaging Biomarker and Lifestyle study of aging. RESULTS: Across all three platforms, the T-tau/Aβ42 ratio biomarker had modestly higher correlation with SUVR/BeCKeT (ρ= 0.69-0.8) as compared with Aβ42 alone (ρ= 0.66-0.75). Differences in CSF biomarker levels between the PET Aβ-amyloid-and Aβ-amyloid+ groups were strongest for the Aβ42/Aβ40 and T-tau/Aβ42 ratios (p < 0.0001); however, comparison of predictive models for PET Aβ-amyloid showed no difference between Aβ42 alone and the T-tau/Aβ42 ratio. CONCLUSION: This study confirms strong concordance between CSF biomarkers and PET Aβ-amyloid status is independent of immunoassay platform, supporting their utility as biomarkers in clinical practice for the diagnosis of AD and for participant enrichment in clinical trials. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/29171991/Concordance_Between_Cerebrospinal_Fluid_Biomarkers_with_Alzheimer's_Disease_Pathology_Between_Three_Independent_Assay_Platforms_ DB - PRIME DP - Unbound Medicine ER -