ABSTRACT
BACKGROUND: Advances in blood biomarker discovery have enabled the improved diagnosis and prognosis of Alzheimer's disease (AD). Most branched-chain amino acids, except isoleucine (Ile), are correlated with both mild cognitive impairment (MCI) and AD. Therefore, this study investigated the association between serum Ile levels and MCI/AD. METHODS: This study stratified 700 participants from the Alzheimer's Disease Neuroimaging Initiative database into four diagnostic groups: cognitively normal, stable MCI, progressive MCI, and AD. Analysis of covariance and chi-square analyses were used to test the demographic data. Receiver operating curve analyses were used to calculate the diagnostic accuracy of different biomarkers and were compared by MedCalc 20. Additionally, Cox proportional hazards models were used to measure the ability of serum Ile levels to predict disease conversion. Finally, a linear mixed-effects model was used to evaluate the associations between serum Ile levels and cognition, brain structure, and metabolism. RESULTS: Serum Ile concentration was decreased in AD and demonstrated significant diagnostic efficacy. The combination of serum Ile and cerebrospinal fluid (CSF) phosphorylated tau (P-tau) improved the diagnostic accuracy in AD compared to total tau (T-tau) alone. Serum Ile levels significantly predicted the conversion from MCI to AD (cutoff value of 78.3 µM). Finally, the results of this study also revealed a correlation between serum Ile levels and the Alzheimer's Disease Assessment Scale cognitive subscale Q4. CONCLUSIONS: Serum Ile may be a potential biomarker of AD. Ile had independent diagnostic efficacy and significantly improved the diagnostic accuracy of CSF P-tau in AD. MCI patients with a lower serum Ile level had a higher risk of progression to AD and a worse cognition assessment.
Subject(s)
Alzheimer Disease , Biomarkers , Cognitive Dysfunction , Isoleucine , tau Proteins , Humans , Cognitive Dysfunction/blood , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/cerebrospinal fluid , Female , Isoleucine/blood , Isoleucine/cerebrospinal fluid , Male , Alzheimer Disease/blood , Alzheimer Disease/diagnosis , Alzheimer Disease/cerebrospinal fluid , Aged , Biomarkers/blood , tau Proteins/blood , tau Proteins/cerebrospinal fluid , Disease Progression , Aged, 80 and over , Proportional Hazards ModelsABSTRACT
BACKGROUND: 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. AIMS: This study aimed to further clarify the characteristics of valine levels in MCI and AD. METHODS: 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. RESULTS: 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. Serum valine was negatively correlated with CSF total tau (t-tau) and phosphorylated tau (p-tau) in pMCI. Serum valine significantly predicted conversion from MCI to AD. In addition, serum valine was related to the rate of change of cerebral glucose metabolism during the follow-up period in pMCI. CONCLUSIONS: 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.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Biomarkers/metabolism , Brain/diagnostic imaging , Brain/metabolism , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/diagnostic imaging , Disease Progression , Glucose , Humans , Positron-Emission Tomography , Valine , tau ProteinsABSTRACT
BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss and cognitive impairment. In 2011, the National Institute on Aging and Alzheimer's Association (NIA-AA) Research Framework has proposed to use biomarkers to diagnose AD in living persons. AD core biomarkers show high diagnostic specificity in distinguishing AD from healthy control subjects, but have little additional value for prognosis or stage of disease. SUMMARY: With the update of detection methods and techniques, other AD biomarkers have been discovered. Neurofilament light (NFL) is currently recognized as a biomarker of nerve axonal injury and one of the candidate markers in AD neurodegeneration, and the relationship between NFL and AD pathophysiology has attracted widespread attention. More and more studies have shown that NFL plays an important role in predicting the clinical progress and prognosis of AD. Recently, the genome-wide association study also found that multiple single-nucleotide polymorphisms are associated with NFL levels and AD risk. Key Messages: In this review, we discuss the relationship between the genetic characteristics of NFL and AD, the NFL levels in AD, and the relationship between NFL and AD core biomarkers, neuroimaging, and cognitive performance.