Serum Sirtuin-1, HMGB1-TLR4, NF-KB and IL-6 Levels in Alzheimer's: The Relation Between Neuroinflammatory Pathway and Severity of Dementia.

Abstract

Alzheimer's disease (AD), which affects the world's aging population, is a progressive neurodegenerative disease requiring markers or tools to accurately and easily diagnose and monitor the process.

Objective: In this study, serum Sirtuin-1(SIRT-1), High Mobility Group Box 1 (HMGB1), Toll-Like Receptor-4 (TLR4), Nuclear Factor Kappa B (NF-kB), Interleukin-6 (IL-6), Amyloid βeta-42 (Aβ- 42), and p-tau181 levels in patients diagnosed with AD according to NINCS-ADRA criteria were studied. We investigated the inflammatory pathways that lead to progressive neuronal loss and highlight their possible relationship with dementia severity in the systemic circulation.

Methods: Patients over 60 years of age were grouped according to their Standard Mini Mental Test results, MRI, and/or Fludeoxyglucose positron emission tomography or according to their CT findings as Control n:20; AD n:32; Vascular Dementia (VD) n:17; AD + VD; n = 21. Complete blood count, Glucose, Vitamin B12, Folic Acid, Enzymes, Urea, Creatinine, Electrolytes, Bilirubin, and Thyroid Function tests were evaluated. ELISA was used for the analysis of serum SIRT1, HMGB1, TLR4, NF-kB, IL-6, Aβ-42, and p-tau181 levels.

Results: Levels of serum Aβ-42, SIRT1, HMGB1, and IL-6 were significantly higher (p< 0.001, p< 0.01, p< 0.001, and p< 0.001, respectively), and TLR4 levels were significantly lower (p< 0.001) in the dementia group than in the control group. No significant difference was observed between dementia and control groups for serum NF-kB and p-tau181 levels.

Conclusion: Our results show that the levels of the Aβ42, SIRT 1, HMGB1, and TLR4 pathways are altered in AD and VD. SIRT 1 activity plays an important role in the inflammatory pathway of dementia development, particularly in AD.