Biochemical Diagnosis of Alzheimer Disease by Measuring the Cerebrospinal Fluid Ratio of Phosphorylated tau Protein to β-Amyloid Peptide[sub 42].

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 β-amyloid peptide[sub 42] (Aβ[sub 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 Aβ[sub 42] as biochemical markers for AD. Methods: We combined CSF measurements of phospho-tau and Aβ[sub 42] 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 Aβ[sub 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 Aβ[sub 42] is superior to either measure alone and can be recommended as an aid to evaluating individuals suspected of having dementia. [ABSTRACT FROM AUTHOR]