Tracing Neurogenetic Pathways: SIRT1 Gene's Influence on Autism, Alzheimer's, Type II Diabetes, Dementia, and its role in Neurodevelopmental Dynamics

Abstract

Background: Autism Spectrum Disorder (ASD) encompasses a range of neurodevelopmental conditions characterized by challenges in social interaction, communication, and repetitive behaviors. Concurrent conditions such as Type II Diabetes Mellitus (DM) and dementia are prevalent comorbidities that exacerbate the cognitive impairments associated with ASD. The SIRT1 gene, known for its role in neuroprotection and longevity, has been implicated in the pathophysiology of these disorders. Objective: To determine the expression of the SIRT1 gene in patients with diabetes and dementia and to investigate its potential as a biomarker for cognitive impairment in these populations. Methods: A cohort of 108 diabetic dementia patients and 32 healthy controls were enrolled. SIRT1 expression levels were quantified using chemiluminescent immunoassay (CLIA) and methylation-specific PCR after bisulfite DNA modification. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and demographic data, along with biochemical parameters such as fasting glucose and HbA1c levels, were analyzed using SPSS version 25. Results: Diabetic dementia patients exhibited significantly lower SIRT1 levels (4.37 ± 1.38 µg/mL) and MMSE scores (12.26 ± 4.56) compared to healthy controls (SIRT1: 11.37 ± 3.64 µg/mL, MMSE: 24.1 ± 3.12). The relative gene expression of SIRT1 in diabetic dementia patients showed a 6.7-fold decrease compared to healthy individuals. Statistical analysis revealed a significant difference in both SIRT1 levels and MMSE scores between the two groups (P<0.05). Conclusion: The underexpression of SIRT1 in diabetic dementia patients and its correlation with lower MMSE scores suggest that SIRT1 could serve as a biomarker for cognitive impairment in this population. The findings advocate for further exploration into SIRT1-targeted interventions, which may improve diagnostics and therapeutic approaches for neurodegenerative conditions associated with ASD.