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Abstract

Objective:

To determine how amyloid β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) levels in CSF behave in a large cohort of patients with different types of dementia.

Methods:

Baseline CSF was collected from 512 patients with Alzheimer disease (AD) and 272 patients with other types of dementia (OD), 135 patients with a psychiatric disorder (PSY), and 275 patients with subjective memory complaints (SMC). Aβ42, t-tau, and p-tau (at amino acid 181) were measured in CSF by ELISA. Autopsy was obtained in a subgroup of 17 patients.

Results:

A correct classification of patients with AD (92%) and patients with OD (66%) was accomplished when CSF Aβ42 and p-tau were combined. Patients with progressive supranuclear palsy had normal CSF biomarker values in 90%. Patients with Creutzfeldt-Jakob disease demonstrated an extremely high CSF t-tau at a relatively normal CSF p-tau. CSF AD biomarker profile was seen in 47% of patients with dementia with Lewy bodies (DLB), 38% in corticobasal degeneration (CBD), and almost 30% in frontotemporal lobar degeneration (FTLD) and vascular dementia (VaD). PSY and SMC patients had normal CSF biomarkers in 91% and 88%. Older patients are more likely to have a CSF AD profile. Concordance between clinical and neuropathologic diagnosis was 85%. CSF markers reflected neuropathology in 94%.

Conclusion:

CSF Aβ42, t-tau, and p-tau are useful in differential dementia diagnosis. However, in DLB, FTLD, VaD, and CBD, a substantial group exhibit a CSF AD biomarker profile, which requires more autopsy confirmation in the future.

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Information & Authors

Information

Published In

Neurology®
Volume 78Number 1January 3, 2012
Pages: 47-54
PubMed: 22170879

Publication History

Received: June 19, 2011
Accepted: August 31, 2011
Published online: December 14, 2011
Published in print: January 3, 2012

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Disclosure

Dr. Schoonenboom, Dr. Reesink, Dr. Verwey, and Dr. Kester report no disclosures. Dr. Teunissen serves on a scientific advisory board for Innogenetics and has a patent pending re: Biomarkers for Alzheimer disease. Dr. Van de Ven and Dr. Pijnenburg report no disclosures. Dr. Blankenstein has received speaker honoraria from Abbott and Ferring and serves as an Associate Editor for Annals of Clinical Biochemistry. Prof. Rozemuller has received research support from the EU FP6 and the International Foundation for Alzheimer Research (ISAO). Dr. Scheltens serves on scientific advisory boards for Danone, Wyeth/Elan Corporation, Bristol-Myers Squibb, Genentech, Inc., Pfizer Inc, and GE Healthcare; has received funding for travel or speaker honoraria from Lundbeck Inc.; served as an Associate Editor of the Journal of Neurology, Neurosurgery & Psychiatry; serves a Book Review Editor for Alzheimer's Disease and Associated Disorders and on the editorial board of Dementia Geriatric Cognitive Disorders; serves as a consultant for Pfizer Inc, GE Healthcare, Avid Radiopharmaceuticals, Inc./Eli Lilly and Company, Genentech, Inc., and Janssen AI; and receives research support from Alzheimer Nederland, the Alzheimer Center, and Stichting VUmc fonds. Dr. Van der Flier reports no disclosures.

Authors

Affiliations & Disclosures

N.S.M. Schoonenboom, MD, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
F.E. Reesink, MD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
N.A. Verwey, MD, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
M.I. Kester, MD, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
C.E. Teunissen, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
P.M. van de Ven, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
Y.A.L. Pijnenburg, MD, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
M.A. Blankenstein, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
A.J. Rozemuller, MD, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
P. Scheltens, MD, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.
W.M. van der Flier, PhD
From the Departments of Neurology (N.S.M.S., N.A.V., M.I.K., Y.A.L.P., P.S., W.M.v.d.F.), Clinical Chemistry (N.A.V., C.E.T., M.A.B.), Pathology (A.J.R.), and Epidemiology and Biostatistics (P.M.v.d.V., W.M.v.d.F.), VU University Medical Center, Alzheimer Center, Amsterdam; and Department of Neurology (F.E.R.), Haga Ziekenhuis, Den Haag, The Netherlands.

Notes

Correspondence and reprint requests to Dr. Schoonenboom: [email protected]

Author Contributions

Dr. Schoonenboom wrote the manuscript and analyzed the data. Dr. Reesink assisted in writing and analyzing the data and contributed equally to this work. Dr. Verwey critically read the manuscript and assisted in writing. Dr. Kester critically read the manuscript and assisted in writing. Dr. Teunissen supervised laboratory examinations and critically read the manuscript. Dr. van de Ven advised and assisted in statistics. Dr. Pijnenburg critically read the manuscript and assisted in writing. Dr. Blankenstein supervised laboratory examinations and critically read the manuscript. Dr. Rozemuller provided background information about the neuropathological data and critically read the manuscript. Dr. Scheltens critically read the manuscript and assisted in writing. Dr. Van der Flier provided the data and assisted in statistics and writing.

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