Open AccessCSF metabolites associate with CSF tau and improve prediction of Alzheimer's disease status
Author(s) -
Dong Ruocheng,
Darst Burcu F.,
Deming Yuetiva,
Ma Yue,
Lu Qiongshi,
Zetterberg Henrik,
Blennow Kaj,
Carlsson Cynthia M.,
Johnson Sterling C.,
Asthana Sanjay,
Engelman Corinne D.
Publication year - 2021
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1002/dad2.12167
Subject(s) - cerebrospinal fluid , lasso (programming language) , etiology , neurofibrillary tangle , alzheimer's disease , alzheimer's disease neuroimaging initiative , disease , medicine , tau protein , psychology , oncology , endocrinology , pathology , neuroscience , senile plaques , world wide web , computer science
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.