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Biochemical Diagnosis of Alzheimer Disease by Measuring the Cerebrospinal Fluid Ratio of Phosphorylated tau Protein to -Amyloid Peptide₄₂

Alessia Maddalena, MD; Andreas Papassotiropoulos, MD; Britta Müller-Tillmanns, MA; Hans H. Jung, MD; Thomas Hegi, MD; Roger M. Nitsch, MD; Christoph Hock, MD

Arch Neurol. 2003;60:1202-1206.

Background  The antemortem diagnosis of Alzheimer disease (AD) requires time-consuming and costly procedures. Therefore, biochemical tests that can direct the physician rapidly to the correct diagnosis are highly desirable. Measurement of single biochemical markers in cerebrospinal fluid (CSF), such as total tau protein and -amyloid peptide₄₂ (A₄₂), shows robust alterations that highly correlate with the clinical diagnosis of AD but generally lack sufficient diagnostic accuracy.

Objective  To study the combination of CSF phosphorylated tau protein (phospho-tau) and A₄₂ as biochemical markers for AD.

Methods  We combined CSF measurements of phospho-tau and A₄₂ in 100 consecutive patients who under-went diagnostic workup for dementia and in 31 healthy control subjects.

Results  We found that the calculated ratio of phospho-tau to A₄₂ was significantly increased in patients with AD and provided high diagnostic accuracy in distinguishing patients with AD from healthy control subjects (sensitivity, 86%; specificity, 97%), subjects with non-AD dementias (sensitivity, 80%; specificity, 73%), and subjects with other neurological disorders (sensitivity, 80%; specificity, 89%).

Conclusion  The diagnostic usefulness of the CSF ratio of phospho-tau to A₄₂ is superior to either measure alone and can be recommended as an aid to evaluating individuals suspected of having dementia.

From the Division of Psychiatry Research, University of Zurich (Drs Maddalena, Papassotiropoulos, Nitsch, and Hock and Ms Müller-Tillmanns); Department of Neurology, University Hospital Zurich (Dr Jung), and Institute for Anesthesiology, University of Zurich (Dr Hegi), Zurich, Switzerland.

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