The Associations of Serum Valine with Mild Cognitive Impairment and Alzheimer’s Disease

Abstract

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.

Longitudinal analysis of UK Biobank participants suggests age and APOE-dependent alterations of energy metabolism in development of dementia

“…If fatty acids are no longer available, amino acids derived from muscle tissue may be used for energy production, further reducing the BMI 39 . On the other hand, we identified an increased level of valine in the brain tissue of the participants with a risk of AD, which is in opposite as their association in the periphery out of blood-brain barrier 10,32,33,[14][15][16]34 . This may be explained by the impaired astrocytes in the early stage of AD, or less inefficient astrocytes in the APOE4 carriers 27 , resulting in a decreased BCAA metabolism in the brain 40 .…”

“…After age 58, valine levels were decreased in APOE4 and APOE33 carriers but not obvious in APOE2 carriers. The association between low levels of valine in the periphery and an increased risk of AD or cognitive dysfunction is well established and has been reported in many studies 10,32,33,[14][15][16]34 . The negative association of valine and BCAAs in blood and dementia is independent from the effect of cardiometabolic disorders, as diabetes, cardiovascular diseases and obesity are associated with higher levels of valine in blood 13,[35][36][37][38] .…”