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

Flora H Duits; Charlotte E Teunissen; Femke H Bouwman; Pieter-Jelle Visser; Niklas Mattsson; Henrik Zetterberg; Kaj Blennow; Oskar Hansson; Lennart Minthon; Niels Andreasen; Jan Marcusson; Anders Wallin; Marcel Olde Rikkert; Magda Tsolaki; Lucilla Parnetti; Sanna-Kaisa Herukka; Harald Hampel; Mony J De Leon; Johannes Schröder; Dag Aarsland; Marinus A Blankenstein; Philip Scheltens; Wiesje M van der Flier

doi:10.1016/j.jalz.2013.12.023

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

Alzheimers Dement. 2014 Nov;10(6):713-723.e2. doi: 10.1016/j.jalz.2013.12.023. Epub 2014 Apr 8.

Authors

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

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / cerebrospinal fluid*
Alzheimer Disease / complications
Alzheimer Disease / diagnosis*
Amyloid beta-Peptides / cerebrospinal fluid*
Analysis of Variance
Apolipoproteins E / genetics
Cognition Disorders / etiology
Cohort Studies
Diagnosis, Differential
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Netherlands
Peptide Fragments / cerebrospinal fluid*
Phosphorylation
ROC Curve
Regression Analysis
tau Proteins / cerebrospinal fluid*

Substances

Amyloid beta-Peptides
Apolipoproteins E
Peptide Fragments
amyloid beta-protein (1-42)
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding