Genetic Polymorphisms in Oxidative Stress and Inflammatory Pathways As Potential Biomarkers in Alzheimer's Disease and Dementia

Oxidative stress and neuroinflammation are important processes involved in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Numerous risk factors, including genetic background, can affect the complex interplay between those mechanisms in the aging brain and can also affect typical AD hallmarks: amyloid plaques and neurofibrillary tangles. Our aim was to evaluate the association of polymorphisms in oxidative stress- and inflammation-related genes with cerebrospinal fluid (CSF) biomarker levels and cognitive test results. The study included 54 AD patients, 14 MCI patients with pathological CSF biomarker levels, 20 MCI patients with normal CSF biomarker levels and 62 controls. Carriers of two polymorphic rs16944 alleles had higher CSF Aβ levels ( = 0.025), while carriers of at least one polymorphic rs35652124 allele had lower CSF Aβ levels ( = 0.040). Association with rs16944 remained significant in the AD group ( = 0.029). Additionally, rs2910164 was associated with Aβ ratio ( = 0.043) in AD. Significant associations with cognitive test scores were observed for rs1001179 ( = 0.022), rs1138272 ( = 0.005), rs1048290 and rs9676881 (both = 0.019), as well as rs35652124 ( = 0.030). In the AD group, rs1071676 ( = 0.004), rs1048290 and rs9676881 (both = 0.035) remained associated with cognitive scores. Polymorphisms in antioxidative and inflammation genes might be associated with CSF biomarkers and cognitive test scores and could serve as additional biomarkers contributing to early diagnosis of dementia.