CSF metabolites associate with CSF tau and improve prediction of Alzheimer's disease status

Abstract

INTRODUCTIONCerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) are biomarkers of Alzheimers disease (AD), yet much is unknown about AD-associated changes in tau metabolism and tau tangle etiology. METHODSWe 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 Alzheimers Disease Research Center, and predicted AD/mild cognitive impairment (MCI) vs. an independent set of older controls using metabolites selected by the least absolute shrinkage and selection operator (LASSO). RESULTSThe 38 CSF metabolites explained 70.3% and 75.7% of the variance in t-tau and p-tau. Of these, 7 LASSO-selected metabolites improved the prediction ability of AD/MCI vs. older controls (AUC score increased from 0.92 to 0.97 and 0.78 to 0.93) compared to the base model. DISCUSSIONThese tau-correlated CSF metabolites increase AD/MCI prediction accuracy and may provide insight into tau tangle etiology.