This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (92)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurology  • Alzheimer Disease  • Psychiatry, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

A Comparative Cerebrospinal Fluid Study

Harald Hampel, MD; Katharina Buerger, MD; Raymond Zinkowski, PhD; Stefan J. Teipel, MD; Alexander Goernitz, MD; Niels Andreasen, MD, PhD; Magnus Sjoegren, MD; John DeBernardis, PhD; Daniel Kerkman, PhD; Koichi Ishiguro, PhD; Hideto Ohno, PhD; Eugeen Vanmechelen, PhD; Hugo Vanderstichele, PhD; Cheryl McCulloch, BS; Hans-Jürgen Möller, MD; Peter Davies, PhD; Kaj Blennow, MD, PhD

Arch Gen Psychiatry. 2004;61:95-102.

Background  Abnormal hyperphosphorylation of the microtubule-associated protein tau and its incorporation into neurofibrillary tangles are major hallmarks of the pathogenesis of Alzheimer disease (AD). Different tau phosphoepitopes can be sensitively detected in cerebrospinal fluid (CSF).

Objective  To compare the diagnostic accuracy of CSF concentrations of tau proteins phosphorylated at 3 pathophysiologically important epitopes (p-tau) to discriminate among patients with AD, nondemented control subjects, and patients with other dementias.

Design and Setting  Cross-sectional, bicenter, memory clinic–based studies.

Participants  One hundred sixty-one patients with a clinical diagnosis of AD, frontotemporal dementia, dementia with Lewy bodies, or vascular dementia and 45 nondemented controls (N = 206).

Main Outcome Measures  Levels of tau protein phosphorylated at threonine 231 (p-tau₂₃₁), threonine 181 (p-tau₁₈₁), and serine 199 (p-tau₁₉₉). The CSF p-tau protein levels were measured using 3 different enzyme-linked immunosorbent assays.

Results  The mean CSF levels of the studied p-tau proteins were significantly elevated in patients with AD compared with the other groups. Applied as single markers, p-tau₂₃₁and p-tau₁₈₁ reached specificity levels greater than 75% between AD and the combined non-AD group when sensitivity was set at 85% or greater. Statistical differences between the assay performances are presented. Particularly, discrimination between AD and dementia with Lewy bodies was maximized using p-tau₁₈₁at a sensitivity of 94% and a specificity of 64%, and p-tau₂₃₁ maximized group separation between AD and frontotemporal dementia with a sensitivity of 88% and a specificity of 92%. Combinations of the 3 markers did not add discriminative power compared with the application as single markers.

Conclusions  The p-tau proteins in CSF come closest to fulfilling the criteria of a biological marker of AD. There is a tendency for p-tau proteins to perform differently in the discrimination of primary dementia disorders from AD.

From the Dementia Research Section and Memory Clinic, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany (Drs Hampel, Buerger, Teipel, Goernitz, and Möller); Applied NeuroSolutions Inc, Vernon Hills, Ill (Drs Zinkowski, DeBernardis, and Kerkman and Ms McCulloch); Karolinska Institute, Neurotec, Division of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden (Dr Andreasen); the Department of Clinical Neuroscience, Unit of Neurochemistry, University of Göteborg, Sahlgren's University Hospital, Mölndal, Sweden (Drs Sjoegren and Blennow); Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan (Dr Ishiguro); Mitsubishi Kagaku Medical, Tokyo (Dr Ohno); Innogenetics NV, Gent, Belgium (Drs Vanmechelen and Vanderstichele); and the Department of Pathology, Albert Einstein College of Medicine, Bronx, NY (Dr Davies). Drs Hampel and Davies are consultants for Applied NeuroSolutions Inc. Drs Zinkowski, DeBernardis, Kerkman, and Davies have stock and employee stock options and Ms McCulloch has employee stock options from Applied NeuroSolutions Inc.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

CSF APPs{alpha} and Phosphorylated Tau Protein Levels in Mild Cognitive Impairment and Dementia of Alzheimer's Type
Fellgiebel et al.
J Geriatr Psychiatry Neurol 2009;22:3-9.
ABSTRACT  

Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies
O'Brien et al.
Br. J. Psychiatry 2009;194:34-39.
ABSTRACT | FULL TEXT  

Variation in MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition
Kauwe et al.
Proc. Natl. Acad. Sci. USA 2008;105:8050-8054.
ABSTRACT | FULL TEXT  

Diagnosis and treatment of dementia: 2. Diagnosis
Feldman et al.
CMAJ 2008;178:825-836.
ABSTRACT | FULL TEXT  

Multicenter assessment of CSF-phosphorylated tau for the prediction of conversion of MCI
Ewers et al.
Neurology 2007;69:2205-2212.
ABSTRACT | FULL TEXT  

No correlation between CSF tau protein phosphorylated at threonine 181 with neocortical neurofibrillary pathology in Alzheimer's disease
Buerger et al.
Brain 2007;130:e82-e82.
FULL TEXT  

Levels of beta-Secretase (BACE1) in Cerebrospinal Fluid as a Predictor of Risk in Mild Cognitive Impairment
Zhong et al.
Arch Gen Psychiatry 2007;64:718-726.
ABSTRACT | FULL TEXT  

CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease
Buerger et al.
Brain 2006;129:3035-3041.
ABSTRACT | FULL TEXT  

Biomarkers in the Diagnosis of Alzheimer's Disease: Are We Ready?
Sunderland et al.
J Geriatr Psychiatry Neurol 2006;19:172-179.
ABSTRACT  

Cerebrospinal Fluid Amyloid {beta}42/Phosphorylated Tau Ratio Discriminates Between Alzheimer's Disease and Vascular Dementia.
de Jong et al.
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2006;61:755-758.
ABSTRACT | FULL TEXT  

Phosphorylated tau predicts rate of cognitive decline in MCI subjects: A comparative CSF study
Buerger et al.
Neurology 2005;65:1502-1503.
FULL TEXT