CSF biomarkers for the differential diagnosis of Alzheimer's disease: A large-scale international multicenter study

Michael Ewers; Niklas Mattsson; Lennart Minthon; José L Molinuevo; Anna Antonell; Julius Popp; Frank Jessen; Sanna-Kaisa Herukka; Hilka Soininen; Walter Maetzler; Thomas Leyhe; Katharina Bürger; Miyako Taniguchi; Katsuya Urakami; Simone Lista; Bruno Dubois; Kaj Blennow; Harald Hampel

doi:10.1016/j.jalz.2014.12.006

CSF biomarkers for the differential diagnosis of Alzheimer's disease: A large-scale international multicenter study

Alzheimers Dement. 2015 Nov;11(11):1306-15. doi: 10.1016/j.jalz.2014.12.006. Epub 2015 Mar 21.

Authors

Michael Ewers¹, Niklas Mattsson², Lennart Minthon³, José L Molinuevo⁴, Anna Antonell⁴, Julius Popp⁵, Frank Jessen⁶, Sanna-Kaisa Herukka⁷, Hilka Soininen⁷, Walter Maetzler⁸, Thomas Leyhe⁹, Katharina Bürger¹⁰, Miyako Taniguchi¹¹, Katsuya Urakami¹², Simone Lista¹³, Bruno Dubois¹⁴, Kaj Blennow¹⁵, Harald Hampel¹³

Affiliations

¹ Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian-University, Munich, Bayern, Germany. Electronic address: [email protected].
² Department of Radiology, University of California San Francisco, San Francisco, CA, USA; Institute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
³ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Neuropsychiatric Clinic, Malmö University Hospital, Malmö, Sweden.
⁴ Alzheimer's disease and other cognitive disorders unit, Neurology Service, ICN Hospital Clinic i Universitari and Pasqual Maragall Foundation, Barcelona, Spain.
⁵ Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Nordrhein-Westfalen, Germany; Department of Psychiatry, University Hospital of Lausanne, Lausanne, Waadt, Switzerland.
⁶ Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Nordrhein-Westfalen, Germany.
⁷ Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
⁸ Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, Center of Neurology, University of Tuebingen, Tuebingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tuebingen, Germany.
⁹ Department of Psychiatry and Psychotherapy, University Hospital, Tübingen, Germany.
¹⁰ Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian-University, Munich, Bayern, Germany.
¹¹ Center of Old Age Psychiatry, Psychiatric University Hospital, Basel, Switzerland.
¹² Department of Biological Regulation, School of Health Science, Tottori University Faculty of Medicine, Yonago, Japan.
¹³ AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d'Alzheimer & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France.
¹⁴ Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d'Alzheimer & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France.
¹⁵ Institute of Neuroscience & Physiology, Department of Psychiatry & Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.

PMID: 25804998
DOI: 10.1016/j.jalz.2014.12.006

Abstract

Introduction: The aim of this study was to test the diagnostic value of cerebrospinal fluid (CSF) beta-amyloid (Aβ1-42), phosphorylated tau, and total tau (tau) to discriminate Alzheimer's disease (AD) dementia from other forms of dementia.

Methods: A total of 675 CSF samples collected at eight memory clinics were obtained from healthy controls, AD dementia, subjective memory impairment, mild cognitive impairment, vascular dementia, Lewy body dementia (LBD), fronto-temporal dementia (FTD), depression, or other neurological diseases.

Results: CSF Aβ1-42 showed the best diagnostic accuracy among the CSF biomarkers. At a sensitivity of 85%, the specificity to differentiate AD dementia against other diagnoses ranged from 42% (for LBD, 95% confidence interval or CI = 32-62) to 77% (for FTD, 95% CI = 62-90).

Discussion: CSF Aβ1-42 discriminates AD dementia from FTD, but shows significant overlap with other non-AD forms of dementia, possibly reflecting the underlying mixed pathologies.

Keywords: Alzheimer's disease; Biomarker; CSF; Cerebrospinal fluid; Classification; Dementia; Differential diagnosis; Fronto-temporal dementia; Lewy body dementia; Vascular dementia.

Publication types

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

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / cerebrospinal fluid*
Alzheimer Disease / diagnosis*
Amyloid beta-Peptides / cerebrospinal fluid*
Biomarkers / cerebrospinal fluid
Diagnosis, Differential
Female
Humans
Internationality
Male
Middle Aged
Peptide Fragments / cerebrospinal fluid*
Phosphorylation
Sensitivity and Specificity
Spinal Puncture
tau Proteins / cerebrospinal fluid*

Substances

Amyloid beta-Peptides
Biomarkers
MAPT protein, human
Peptide Fragments
amyloid beta-protein (1-42)
tau Proteins