NeuroGenetics of Alzheimer’s Disease: Crosslinking SIRT1 Gene in the Genetic Nexus of Type II Diabetes and Dementia

Abstract

Background: Background: Type II Diabetes Mellitus (DM) is a chronic condition that not only affects organ function but also contributes to the development of dementia. SIRT1, a gene implicated in the pathophysiology of Type II DM, has been associated with neurodegenerative processes and cognitive decline. Objective: This study aimed to evaluate the expression of the SIRT1 gene in patients with Type II DM and dementia, elucidating its potential role as a biomarker for cognitive impairment and neurodegeneration in this population. Methods: A cohort of 88 diabetic patients with dementia and 12 healthy controls were recruited, and EDTA blood samples were collected. SIRT1 serum levels were quantified using chemiluminescent immunoassay (CLIA). Genomic DNA was extracted and assessed for quality before bisulfite DNA modification and Methylation Specific PCR (MSP) to profile SIRT1 gene methylation. Real-time PCR was conducted to determine SIRT1 gene expression levels. Cognitive function was assessed using Mini-Mental State Examination (MMSE) scores. Results: The average SIRT1 serum levels in diabetic dementia patients (4.98 ± 1.38 µg/mL) were significantly lower than those in healthy controls (14.21 ± 3.64 µg/mL). MMSE scores mirrored this trend, with patients scoring 12.26 ± 4.56, indicating more considerable cognitive impairment compared to healthy controls' score of 24.1 ± 3.12. SIRT1 gene expression was found to be underexpressed with a fold decrease of approximately 4.1 in dementia cases. Conclusion: The study's findings highlight the downregulated expression of the SIRT1 gene in diabetic patients with dementia, confirming its potential as a biomarker for cognitive decline. Identifying SIRT1 alterations may provide a non-invasive approach for early diagnosis and management of dementia in the diabetic population.