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

BACKGROUND: Mild cognitive impairment (MCI) sits between normal aging and Alzheimer disease (AD). Identification of accessible serum biomarkers linked with Alzheimer pathology may facilitate early detection and intervention, potentially delaying disease progression. OBJECTIVE: To explore the associations between serum sirtuin-3 (SIRT3) levels in individuals with MCI with AD pathological markers related to cognitive function. METHODS: This prospective observational study included 106 participants with MCI and 100 age- and sex-matched cognitively healthy controls (HC). We quantified SIRT3, inflammatory cytokines (IL-6 and IL-17), and AD biomarkers (Aβ40, Aβ42, and p-Tau) by enzyme-linked immunosorbent assay. We used standardized neuropsychological tests to assess cognitive function. Logistic regression and receiver operating characteristic curve analyses were conducted to evaluate the diagnostic potential of serum SIRT3. RESULTS: SIRT3 levels were significantly lower in individuals with MCI compared to HC (p < 0.05). Individuals with MCI exhibited decreased serum Aβ42, reduced Aβ42/Aβ40 ratio, and increased p-Tau levels (p < 0.05). SIRT3 levels were positively correlated with cognitive performance scores, positively associated with Aβ42 and Aβ42/Aβ40 ratio, and negatively correlated with p-Tau levels. Receiver operating characteristic curve analysis demonstrated that SIRT3 had promising diagnostic value in differentiating individuals with MCI from HC. Logistic regression analysis identified lower SIRT3 levels, reduced Aβ42, and a decreased Aβ42/Aβ40 ratio as significant independent risk factors for MCI. CONCLUSION: Reduced SIRT3 levels were associated with cognitive impairment and AD biomarkers in individuals with MCI, suggesting that SIRT3 might serve as a novel, minimally invasive adjunctive biomarker for early identification of MCI.