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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)