Genetic polymorphisms in oxidative stress and inflammatory pathways as potential biomarkers in Alzheimer’s disease and dementia

Vogrinc, David (author), Gregorič Kramberger, Milica (author), Emeršič, Andreja (author), Čučnik, Saša (author), Goričar, Katja (author), Dolžan, Vita (author)

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.

• Language: English
• Keywords: Alzheimer’s disease, oxidative stress, inflammation, polymorphism, biomarker
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 22 str.
• Numbering: Vol. 12, iss. 2, art. 316
• PID: 20.500.12556/RUL-154046
• UDC: 616.8
• ISSN on article: 2076-3921
• DOI: 10.3390/antiox12020316
• COBISS.SI-ID: 139886083
• Publication date in RUL: 22.01.2024

Record is a part of a journal

• Title: Antioxidants
• Shortened title: Antioxidants
• Publisher: MDPI
• ISSN: 2076-3921
• COBISS.SI-ID: 522976025

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: Alzheimerjeva bolezen, oksidativni stres, vnetje

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku