Imagine your brain as a bustling city, and the metabolic profiling of cerebrospinal fluid (CSF) and blood serum as a detailed map of its inner workings. In this study, scientists used cutting-edge technology to analyze the levels of various metabolites in the CSF and serum of patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Just like detectives deciphering clues to solve a mystery, these researchers unveiled intriguing patterns and differences between healthy individuals and those with cognitive decline.

One of the key findings was a significant reduction in acetoacetate, a ketone body, in both CSF and serum of AD and MCI patients. This suggests an altered metabolism in these individuals, potentially linked to the progression of dementia. Additionally, the researchers identified changes in other metabolites, such as valine and 2-hydroxybutyrate, that may serve as potential biomarkers for distinguishing between AD and MCI.

By considering different sexes, the scientists found sex-specific variations in metabolic profiles. Male AD patients showed decreased levels of 2-hydroxybutyrate and acetoacetate in their CSF, while female AD patients had increased levels of serum creatinine. These intriguing sex-specific differences further emphasize the complex nature of these diseases and highlight the importance of personalized approaches to diagnosis and treatment.

This groundbreaking study not only expands our knowledge of the metabolic alterations associated with dementia but also holds promise for developing new diagnostic tools and interventions. Don your scientific cap and read the full research article to delve deeper into this exciting field!

BackgroundBeta-amyloid (Abeta) and tau protein in cerebrospinal fluid (CSF) are established diagnostic biomarkers for Alzheimer’s disease (AD). However, these biomarkers may not the only ones existing parameters that reflect Alzheimer’s disease neuropathological change. The use of quantitative metabolomics approach could provide novel insights into dementia progression and identify key metabolic alterations in CSF and serum.MethodsIn the present study, we quantified a set of 45 metabolites in CSF (71 patients) and 27 in serum (76 patients) in patients with mild cognitive impairment (MCI), AD, and controls using nuclear magnetic resonance (NMR)-based metabolomics.ResultsWe found significantly reduced CSF (1.32-fold, p = 0.0195) and serum (1.47-fold, p = 0.0484) levels of the ketone body acetoacetate in AD and MCI patients. Additionally, we found decreased levels (1.20-fold, p = 0.0438) of the branched-chain amino acid (BCAA) valine in the CSF of AD patients with increased valine degradation pathway metabolites (such as 3-hydroxyisobutyrate and α-ketoisovalerate). Moreover, we discovered that CSF 2-hydroxybutyrate is dramatically reduced in the MCI patient group (1.23-fold, p = 0.039). On the other hand, vitamin C (ascorbate) was significantly raised in CSF of these patients (p = 0.008). We also identified altered CSF protein content, 1,5-anhydrosorbitol and fructose as further metabolic shifts distinguishing AD from MCI. Significantly decreased serum levels of the amino acid ornithine were seen in the AD dementia group when compared to healthy controls (1.36-fold, p = 0.011). When investigating the effect of sex, we found for AD males the sign of decreased 2-hydroxybutyrate and acetoacetate in CSF while for AD females increased serum creatinine was identified.ConclusionQuantitative NMR metabolomics of CSF and serum was able to efficiently identify metabolic changes associated with dementia groups of MCI and AD patients. Further, we showed strong correlations between these changes and well-established metabolomic and clinical indicators like Abeta.

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