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Serum SIRT3 Levels and Their Relationship With Alzheimer Disease Pathological Markers in Individuals With Mild

Jing Du1,2, Zexin An3, Xiaoning Niu1

  • 1Departments of Neurology.

Cognitive and Behavioral Neurology : Official Journal of the Society for Behavioral and Cognitive Neurology
|June 18, 2026
PubMed
Abstract

Insights

Serum sirtuin-3 (SIRT3) levels are lower in mild cognitive impairment (MCI) and linked to Alzheimer

Area of Science:

  • Neuroscience and Aging Research
  • Biomarker Discovery for Neurodegenerative Diseases

Background:

  • Mild cognitive impairment (MCI) represents a transitional stage between normal aging and Alzheimer's disease (AD).
  • Early identification of accessible serum biomarkers is crucial for timely intervention in AD pathology.
  • Alzheimer's disease biomarkers, including amyloid-beta (Aβ) and tau proteins, are key indicators of disease progression.

Purpose of the Study:

  • To investigate the association between serum sirtuin-3 (SIRT3) levels and cognitive function in individuals with MCI.
  • To explore the relationship between serum SIRT3 and established Alzheimer's disease pathological markers.
  • To evaluate the diagnostic potential of serum SIRT3 for differentiating MCI from healthy controls.

Main Methods:

  • Prospective observational study involving 106 participants with MCI and 100 healthy controls (HC).
  • Quantification of serum SIRT3, inflammatory cytokines (IL-6, IL-17), and AD biomarkers (Aβ40, Aβ42, p-Tau) using ELISA.
  • Neuropsychological testing for cognitive assessment, alongside logistic regression and ROC curve analyses for diagnostic evaluation.

Main Results:

  • Significantly lower SIRT3 levels were observed in individuals with MCI compared to HC (p < 0.05).
  • MCI participants showed decreased serum Aβ42, reduced Aβ42/Aβ40 ratio, and elevated p-Tau levels (p < 0.05).
  • SIRT3 levels positively correlated with cognitive performance and Aβ42/Aβ40 ratio, and negatively with p-Tau; ROC analysis indicated diagnostic value for SIRT3.

Conclusions:

  • Reduced serum SIRT3 levels are associated with cognitive impairment and AD biomarkers in MCI.
  • SIRT3 may serve as a novel, minimally invasive adjunctive biomarker for the early detection of MCI.
  • Further research can explore SIRT3's role in disease progression and therapeutic strategies for MCI and AD.
Keywords:
Alzheimer diseaseamyloid-betabiomarkersmild cognitive impairmentsirtuin-3tau protein

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