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

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. © 2021 The Authors.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
Alzheimer’s disease
Cerebrospinal fluid
Metabolite
Metabolomics
P-tau
T-tau
1 myristoyl 2 palmitoyl gpc
1 oleoyl gpc
1 palmitoyl gpc
arabinitol
arabinose
biological marker
C glycosyl tryptophan
glucuronic acid
gulonate
n acetylneuraminate
nucleotide derivative
pentose
tau protein
tryptophan
unclassified drug
x 10457
x 24228
xylitol
adult
aged
Alzheimer disease
Article
biological functions
clinical outcome
cognitive defect
cohort analysis
controlled study
female
glycerophospholipid metabolism
groups by age
human
major clinical study
male
middle aged
phospholipid metabolism
prediction
protein blood level
protein cerebrospinal fluid level
protein phosphorylation
sex difference
variance

Darst, B. F. (author)
Deming, Y. (author)
Ma, Y. (author)
Lu, Q. (author)
Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xzethe (author)
Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xbleka (author)
Carlsson, C. M. (author)
Johnson, S. C. (author)
Asthana, S. (author)
Engelman, C. D. (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi (creator_code:org_t)

In:Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring: Wiley13:12352-8729

By the author/editor: Dong, R.; Darst, B. F.; Deming, Y.; Ma, Y.; Lu, Q.; Zetterberg, Henr ...; show more...; Blennow, Kaj, 19 ...; Carlsson, C. M.; Johnson, S. C.; Asthana, S.; Engelman, C. D.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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