Csf metabolites associate with csf tau and improve prediction of alzheimer’s disease status

Abstract

Introduction: Cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) are biomarkers of Alzheimer’s disease (AD), yet much is unknown about AD-associated changes in tau metabolism and tau tangle etiology. Methods: We assessed the variation of t-tau and p-tau explained by 38 previously identified CSF metabolites using linear regression models in middle-age controls from the Wisconsin Alzheimer’s Disease Research Center, and predicted AD/mild cognitive impairment (MCI) versus an independent set of older controls using metabolites selected by the least absolute shrinkage and selection operator (LASSO). Results: The 38 CSF metabolites explained 70.3% and 75.7% of the variance in t-tau and p-tau, respectively. Of these, seven LASSO-selected metabolites improved the prediction ability of AD/MCI versus older controls (area under the curve score increased from 0.92 to 0.97 and 0.78 to 0.93) compared to the base model. Discussion: These tau-correlated CSF metabolites increase AD/MCI prediction accuracy and may provide insight into tau tangle etiology.