Blood-based biomarkers in Alzheimer’s disease – moving towards a new era of diagnostics

Arslan, Burak; Zetterberg, Henrik; Ashton, Nicholas J.

doi:10.1515/cclm-2023-1434

Cited by 6 publications

(1 citation statement)

References 62 publications

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“…Future longitudinal studies on larger elderly cohorts adopting a multidimensional approach, including the measurement of blood biomarkers mirroring brain (e.g. neuro lament light chain, Aβ42/Aβ40 ratio, phosphorylated tau 94 ) and peripheral organs damage, as well as in ammation, are warranted to elucidate this issue. Second, the sex ratio was unbalanced with an higher prevalence of females, potentially biasing the analyses conducted after stratifying the cohort by sex.…”

Section: Discussionmentioning

confidence: 99%

Serum D-serine to total serine ratio and glycine levels as predictive biomarkers for cognitive dysfunction in frail elderly subjects

Imarisio,

Yahyavi,

Gasparri

et al. 2024

Preprint

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Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors and huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms concurring to determine frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine and D-serine, as well as their precursors L-glutamine, L-asparagine and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher glycine levels and D-/Total serine correlated with worse cognition and depressive symptoms in the frail group. These findings suggest that altered homeostasis of D-serine may represent a biochemical signature of frailty, while increased serum glycine and D-/Total serine ratio could be specifically associated with cognitive decline and depression in frail older populations.

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Section: Discussionmentioning

confidence: 99%

Serum D-serine to total serine ratio and glycine levels as predictive biomarkers for cognitive dysfunction in frail elderly subjects

Imarisio,

Yahyavi,

Gasparri

et al. 2024

Preprint

View full text Add to dashboard Cite

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Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects

Imarisio,

Yahyavi,

Gasparri

et al. 2024

Transl Psychiatry

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Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High-Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine, and D-serine, as well as their precursors L-glutamine, L-asparagine, and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle, and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty.

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Pre-Diagnosis Observational and Prescription History associated with Alzheimer’s Disease Incidence

Williams

2024

Preprint

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BackgroundAlzheimer’s disease (AD) has so far proved refractory to intervention. However, disease incidence is variable across prior medication and observational measures. The present study adopted a data-driven approach to inform possible drug repurposing strategies in the light of concurrent prescription and biometric data.Methods and ResultsA real-world dataset was harnessed to compare observational and prescription data for 250,000 individuals prior to AD diagnosis against an age-, sex-, and clinical practice-matched control cohort with no AD history. Observation data was shown to both explain the associations of classes of drug prescription with AD incidence and to bolster the repurposing potential of the GLP-1 agonist class of anti-diabetic drugs.ConclusionThis study provides insights into how drug repurposing based on prescription histories can be informed by concurrent observational data. These findings offer novel insights to be explored in future research on causal models for AD progression.

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Blood-based biomarkers in Alzheimer’s disease – moving towards a new era of diagnostics

Cited by 6 publications

References 62 publications

Serum D-serine to total serine ratio and glycine levels as predictive biomarkers for cognitive dysfunction in frail elderly subjects

Serum D-serine to total serine ratio and glycine levels as predictive biomarkers for cognitive dysfunction in frail elderly subjects

Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects

Pre-Diagnosis Observational and Prescription History associated with Alzheimer’s Disease Incidence

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