Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to β-amyloid peptide42

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 beta-amyloid peptide(42) (Abeta(42)), 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 Abeta(42), as biochemical markers for AD. Methods: We combined CSF measurements of phosphotau and Abeta(42) in 100 consecutive patients who underwent diagnostic workup for dementia and in 31 healthy control subjects. Results: We found that the calculated ratio of phosphotau to Abeta(42) 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 Abeta(42) is superior to either measure alone and can be recommended as an aid to evaluating individuals suspected of having dementia.