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 Schroeder; 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?

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 Schroeder
, Dag Aarsland

Marinus A. Blankenstein, Philip Scheltens, Wiesje M. van der Flier

^*Corresponding author for this work

MHeNs - Cognitive Neuropsychiatry and Clinical Neuroscience

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), 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/A beta(42) ratio and 0.08 for the p-tau/A beta(42) 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/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of >0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.

Original language	English
Pages (from-to)	713-723
Journal	Alzheimer's & Dementia
Volume	10
Issue number	6
DOIs	https://doi.org/10.1016/j.jalz.2013.12.023
Publication status	Published - Nov 2014

Keywords

Dementia
Alzheimer's disease
Mild cognitive impairment
Cerebrospinal fluid
Amyloid-beta(1-42)
Tau
Biomarkers
Differential diagnosis
Predictive value

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10.1016/j.jalz.2013.12.023

Cite this

Duits, F. H., Teunissen, C. E., Bouwman, F. H., Visser, P.-J., Mattsson, N., Zetterberg, H., Blennow, K., Hansson, O., Minthon, L., Andreasen, N., Marcusson, J., Wallin, A., Rikkert, M. O., Tsolaki, M., Parnetti, L., Herukka, S.-K., Hampel, H., De Leon, M. J., Schroeder, J., ... van der Flier, W. M. (2014). The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean? Alzheimer's & Dementia, 10(6), 713-723. https://doi.org/10.1016/j.jalz.2013.12.023

@article{a3c78e5fcdc84de49d517351173f00c8,

title = "The cerebrospinal fluid {"}Alzheimer profile{"}: Easily said, but what does it mean?",

abstract = "Background: We aimed to identify the most useful definition of the {"}cerebrospinal fluid Alzheimer profile,{"} based on amyloid-beta(1-42) (A beta(42)), 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/A beta(42) ratio and 0.08 for the p-tau/A beta(42) 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/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of >0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers. ",

keywords = "Dementia, Alzheimer's disease, Mild cognitive impairment, Cerebrospinal fluid, Amyloid-beta(1-42), Tau, Biomarkers, Differential diagnosis, Predictive value",

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

year = "2014",

month = nov,

doi = "10.1016/j.jalz.2013.12.023",

language = "English",

volume = "10",

pages = "713--723",

journal = "Alzheimer's \& Dementia",

issn = "1552-5260",

publisher = "John Wiley \& Sons Inc.",

number = "6",

}

Duits, FH, Teunissen, CE, Bouwman, FH, Visser, P-J, Mattsson, N, Zetterberg, H, Blennow, K, Hansson, O, Minthon, L, Andreasen, N, Marcusson, J, Wallin, A, Rikkert, MO, Tsolaki, M, Parnetti, L, Herukka, S-K, Hampel, H, De Leon, MJ, Schroeder, J, Aarsland, D, Blankenstein, MA, Scheltens, P & van der Flier, WM 2014, 'The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?', Alzheimer's & Dementia, vol. 10, no. 6, pp. 713-723. https://doi.org/10.1016/j.jalz.2013.12.023