Sharpen That Needle

The article by De Meyer et al¹ in this month's issue of the Archives presents a novel method of analyzing cerebrospinal fluid (CSF) biomarker data and determining how these data map onto the clinical diagnoses of Alzheimer disease (AD), mild cognitive impairment (MCI), and healthy control subjects. Using a 2-component mixture model, they identified a signature of low β-amyloid 1-42 (Aβ1-42) level, high total tau protein (T-tau) level, and elevated phosphorylated tau protein 181 (P-tau 181) level that was detected in more than 90% of the AD group and only 39% of the control group; the MCI group was intermediate with 73%. Overall, the diagnostic sensitivity was 90% for AD with a specificity of 64% in 3 independent data sets. Further, the AD CSF signature of low Aβ1-42 level and high P-tau 181 level correctly identified 100% of MCI cases that progressed to AD within 5 years. This report solidifies the diagnostic importance of measuring Aβ, T-tau, and P-tau in CSF² and confirms the value of CSF measurements in predicting the conversion of MCI to AD.³