NeuroGenetics of Alzheimer’s Disease: Cross-Linking BDNF Brain-Derived Neurotrophic Factor in the Genetic Nexus of Type II Diabetes and Dementia

Abstract

Background: Alzheimer’s disease and dementia are commonly associated with aging, particularly in the context of Type II Diabetes Mellitus (Type II DM), which is known to exacerbate micro and macrovascular complications that affect cognitive functions. The Brain-Derived Neurotrophic Factor (BDNF) gene has been implicated in the neurodegenerative processes that underscore these conditions. Objective: This study aimed to investigate the expression of the BDNF gene in diabetic patients with dementia and analyze its correlation with cognitive impairment, to establish BDNF as a potential biomarker for early detection and therapeutic targeting. Methods: A cohort of 102 patients with diabetic dementia and 32 healthy controls was enrolled. EDTA blood samples were collected and processed to measure BDNF serum levels using a Chemiluminescent Immunoassay (CLIA). Genomic DNA was isolated, and its integrity was confirmed via UV spectrophotometry and gel electrophoresis. The bisulfite DNA modification and Methylation-Specific PCR were conducted to analyze BDNF gene expression, followed by quantitative real-time PCR. Cognitive function was assessed using Mini-Mental State Examination (MMSE). Results: The study revealed a significant decrease in BDNF serum levels in diabetic dementia patients (12.6 ng/mL) compared to healthy controls (34.8 ng/mL), with MMSE scores averaging at 13.2 and 24.6, respectively. BDNF gene expression showed a 4.1-fold decrease in the dementia group. Statistical analysis indicated that these differences were significant (p<0.05). Conclusion: The reduced expression of BDNF in patients with diabetic dementia confirms its potential as a biomarker for cognitive impairment. Early detection and intervention strategies that modulate BDNF could ameliorate the impact of dementia in the context of diabetes.