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



We aimed to investigate the inflammatory pathways that lead to progressive neuronal loss and highlight their possible relationship with dementia severity by detecting these molecules in the systemic circulation.



Since neuronal loss and neuropathological lesion formation reach an irreversible stage by the time of diagnosis, symptomatic treatments that are applied can only offer modest clinical outcomes. This necessitates the search for a marker or tool to diagnose and monitor the process accurately and easily.



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), Interleukine-6 (IL-6), Amyloid βeta-42 (Aβ-42), and p-tau181 levels in patients diagnosed with AD according to NINCS-ADRA criteria were studied.



Patients over 60 years of age were grouped according to their Standard Mini Mental Test, MRI, and/or Fludeoxyglucose positron emission tomography or according to their Computed Tomography 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, Uric Acid levels, Creatinine, Electrolytes, Bilirubin, Thyroid Function tests, and Sedimentation rate were evaluated. ELISA kit method was used for the analysis of serum SIRT1, HMGB1, TLR4, NF-kB, IL-6, Aβ-42, and p-tau181 levels.



Levels of serum Aβ-42, SIRT1, HMGB1, and IL-6 were significantly higher (p˂0.001, p&amp;lt;0.01, p&amp;lt;0.001, and p&amp;lt;0.001, respectively), and TLR4 levels were significantly lower (p˂0.001) in the dementia group than in the control group. There was no significant difference between dementia and control groups for serum NF-kB and p-tau181 levels.



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 Alzheimer&#039;s disease.



This work is financially supported by Cerrahpaşa Scientific Research Projects Coordination Unit (BAPSİS)
