The introduction of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in Alzheimer's disease (AD). Recent studies have found that the levels of valine are related to mild cognitive impairment (MCI) and AD, but its characteristics in MCI and AD need to be further clari ed. A total of 786 participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) cohort were selected to evaluate the relationships between serum valine and cerebrospinal uid (CSF) biomarkers, brain structure (magnetic resonance imaging, MRI), cerebral glucose metabolism ( 18 F-uorodeoxyglucose-positron emission tomography, FDG-PET), and cognitive declines, through different cognitive subgroups. We found that (1) serum valine was decreased in patients with AD compared with cognitive normal (CN) and stable MCI (sMCI), and in progressive MCI (pMCI) compared with CN; (2) serum valine was negatively correlated with CSF total tau (t-tau) and phosphorylated tau (p-tau) in pMCI; (3) serum valine signi cantly predicted conversion from MCI to AD; (4) serum valine was related to the rate of change of cerebral glucose metabolism during the follow-up period in pMCI. We speculated serum valine may be a peripheral biomarker of pMCI and AD, and its level predicts the progression of MCI to AD. Our study may help to reveal the metabolic changes during AD disease trajectory and its relationship to clinical phenotype.

The introduction of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in Alzheimer’s disease (AD). Recent studies have found that the levels of valine are related to mild cognitive impairment (MCI) and AD, but its characteristics in MCI and AD need to be further clarified. A total of 786 participants from the Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI-1) cohort were selected to evaluate the relationships between serum valine and cerebrospinal fluid (CSF) biomarkers, brain structure (magnetic resonance imaging, MRI), cerebral glucose metabolism (18F-fluorodeoxyglucose-positron emission tomography, FDG-PET), and cognitive declines, through different cognitive subgroups. We found that (1) serum valine was decreased in patients with AD compared with cognitive normal (CN) and stable MCI (sMCI), and in progressive MCI (pMCI) compared with CN; (2) serum valine was negatively correlated with CSF total tau (t-tau) and phosphorylated tau (p-tau) in pMCI; (3) serum valine significantly predicted conversion from MCI to AD; (4) serum valine was related to the rate of change of cerebral glucose metabolism during the follow-up period in pMCI. We speculated serum valine may be a peripheral biomarker of pMCI and AD, and its level predicts the progression of MCI to AD. Our study may help to reveal the metabolic changes during AD disease trajectory and its relationship to clinical phenotype.