Genetic Polymorphisms in Oxidative Stress and Inflammatory Pathways as Potential Biomarkers in Alzheimer's Disease and Dementia.
David VogrincMilica Gregorič KrambergerAndreja EmeršičSaša ČučnikKatja GoričarVita DolzanPublished in: Antioxidants (Basel, Switzerland) (2023)
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 IL1B rs16944 alleles had higher CSF Aβ 1-42 levels ( p = 0.025), while carriers of at least one polymorphic NFE2L2 rs35652124 allele had lower CSF Aβ 1-42 levels ( p = 0.040). Association with IL1B rs16944 remained significant in the AD group ( p = 0.029). Additionally, MIR146A rs2910164 was associated with Aβ 42/40 ratio ( p = 0.043) in AD. Significant associations with cognitive test scores were observed for CAT rs1001179 ( p = 0.022), GSTP1 rs1138272 ( p = 0.005), KEAP1 rs1048290 and rs9676881 (both p = 0.019), as well as NFE2L2 rs35652124 ( p = 0.030). In the AD group, IL1B rs1071676 ( p = 0.004), KEAP1 rs1048290 and rs9676881 (both p = 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.
Keyphrases
- mild cognitive impairment
- oxidative stress
- cognitive decline
- cerebrospinal fluid
- risk factors
- multiple sclerosis
- dna damage
- ischemia reperfusion injury
- cell proliferation
- cognitive impairment
- gene expression
- ejection fraction
- diabetic rats
- long noncoding rna
- subarachnoid hemorrhage
- inflammatory response
- anti inflammatory
- patient reported outcomes
- cerebral ischemia
- genome wide identification