The cerebrospinal fluid "Alzheimer profile": easily said, but what does it mean?

Flora H Duits¹, Charlotte E Teunissen², Femke H Bouwman³, Pieter-Jelle Visser⁴, Niklas Mattsson⁵, Henrik Zetterberg⁶, Kaj Blennow⁷, Oskar Hansson⁸, Lennart Minthon⁸, Niels Andreasen⁹, Jan Marcusson¹⁰, Anders Wallin⁷, Marcel Olde Rikkert¹¹, Magda Tsolaki¹², Lucilla Parnetti¹³, Sanna-Kaisa Herukka¹⁴, Harald Hampel¹⁵, Mony J De Leon¹⁶, Johannes Schröder¹⁷, Dag Aarsland¹⁸, Marinus A Blankenstein², Philip Scheltens³, Wiesje M van der Flier¹⁹

Affiliations

¹ Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: F.Duits@vumc.nl.
² Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
³ Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
⁴ Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Department of Psychiatry and Neuropsychology, Institute of Brain and Behaviour, University of Maastricht, Maastricht, The Netherlands.
⁵ Department of Neurochemistry and Psychiatry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
⁶ Department of Neurochemistry and Psychiatry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, UK.
⁷ Department of Neurochemistry and Psychiatry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
⁸ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
⁹ KI-Alzheimer Disease Research Centre, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
¹⁰ Division of Geriatric Medicine, Department of Neuroscience and Locomotion, Linköping University, Linköping, Sweden.
¹¹ Donders Institute for Brain Cognition and Behaviour, Radboud Alzheimer Center, Nijmegen, The Netherlands.
¹² Memory and Dementia Centre, 3rd Department of Neurology, Aristotle University of Thessaloniki, "G. Papanicolaou" General Hospital, Thessaloniki, Greece.
¹³ Clinica Neurologica, University of Perugia, Perugia, Italy.
¹⁴ Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
¹⁵ Département de Neurologie & Institut de la Mémoire et de la Maladie d'Alzheimer Pavillon, Université Pierre et Marie Curie, François Lhermitte Hôpital de la Salpêtrière, Paris, France.
¹⁶ Center for Brain Health, New York University, School of Medicine, New York, NY, USA.
¹⁷ Sektion Gerontopsychiatrie, Universität Heidelberg, Heidelberg, Germany.
¹⁸ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
¹⁹ Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.

PMID: 24721526
DOI: 10.1016/j.jalz.2013.12.023

The cerebrospinal fluid "Alzheimer profile": easily said, but what does it mean?

Flora H Duits et al. Alzheimers Dement. 2014 Nov.

. 2014 Nov;10(6):713-723.e2.

doi: 10.1016/j.jalz.2013.12.023. Epub 2014 Apr 8.

Authors

Affiliations

¹ Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: F.Duits@vumc.nl.
² Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
³ Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
⁴ Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Department of Psychiatry and Neuropsychology, Institute of Brain and Behaviour, University of Maastricht, Maastricht, The Netherlands.
⁵ Department of Neurochemistry and Psychiatry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
⁶ Department of Neurochemistry and Psychiatry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, UK.
⁷ Department of Neurochemistry and Psychiatry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
⁸ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
⁹ KI-Alzheimer Disease Research Centre, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
¹⁰ Division of Geriatric Medicine, Department of Neuroscience and Locomotion, Linköping University, Linköping, Sweden.
¹¹ Donders Institute for Brain Cognition and Behaviour, Radboud Alzheimer Center, Nijmegen, The Netherlands.
¹² Memory and Dementia Centre, 3rd Department of Neurology, Aristotle University of Thessaloniki, "G. Papanicolaou" General Hospital, Thessaloniki, Greece.
¹³ Clinica Neurologica, University of Perugia, Perugia, Italy.
¹⁴ Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
¹⁵ Département de Neurologie & Institut de la Mémoire et de la Maladie d'Alzheimer Pavillon, Université Pierre et Marie Curie, François Lhermitte Hôpital de la Salpêtrière, Paris, France.
¹⁶ Center for Brain Health, New York University, School of Medicine, New York, NY, USA.
¹⁷ Sektion Gerontopsychiatrie, Universität Heidelberg, Heidelberg, Germany.
¹⁸ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
¹⁹ Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.

PMID: 24721526
DOI: 10.1016/j.jalz.2013.12.023

Abstract

Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-ß1-42 (Aβ42), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimer's disease (AD).

Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442).

Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/Aβ42 ratio and 0.08 for the p-tau/Aβ42 ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/Aβ42 ratio.

Conclusions: A tau/Aβ42 ratio of >0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.

Keywords: Alzheimer's disease; Amyloid-β(1-42); Biomarkers; Cerebrospinal fluid; Dementia; Differential diagnosis; Mild cognitive impairment; Predictive value; Tau.

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Can we rely only on ratios of cerebrospinal fluid biomarkers for AD biological diagnosis?
Lehmann S, Gabelle A, Paquet C. Lehmann S, et al. Alzheimers Dement. 2015 Sep;11(9):1125-6. doi: 10.1016/j.jalz.2014.09.003. Epub 2014 Nov 15. Alzheimers Dement. 2015. PMID: 25457432 No abstract available.

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The cerebrospinal fluid "Alzheimer profile": easily said, but what does it mean?

Affiliations

The cerebrospinal fluid "Alzheimer profile": easily said, but what does it mean?

Authors

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Abstract

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