Projects_laboratory_brm

Study of Peripheral inflammatory biomarkers in association with inflammation-related genes polymorphisms and APOE4 genotype in Alzheimer's patients

2023-03-26 23:46
Project goal
The project goal is to study the expression levels of pro-inflammatory and anti-inflammatory cytokines in blood serum in association with APOE genotype and inflammation-related gene polymorphisms in DNA samples isolated from AD patients and age- and sex-matched healthy individuals.

Project tasks:
  1. Study of APOE genotypes in DNA samples isolated from the peripheral blood of patients with dementia and the control group
  2. Study of serum pro-inflammatory and anti-inflammatory cytokine levels, as well as blood inflammatory profiles in the patients diagnosed with AD and the control group
  3. Evaluation of inflammation-related genes polymorphisms in DNA samples isolated from the peripheral blood of patients with dementia and the control group
  4. Study the associations between APOE genotype, inflammation-related genes polymorphisms, and pro-inflammatory and anti-inflammatory cytokines and chemokines levels in patients with dementia and the control group. Our special focus of interest is a comparative analysis of the inflammation-related gene polymorphisms in APOE4 carriers with and without dementia.

Abstract: Over the last decade, it become evident that chronic peripheral inflammation is one of the important factors contributing significantly to the development and progression of Alzheimer’s disease (AD), and that chronic inflammation in AD involves innate immune cells and inflammatory mediators, such as cytokines and chemokines. However, despite increasing evidence supporting the association between abnormal inflammation and AD, no well-established inflammatory biomarkers are currently available for AD and there has been a sparse expansion of inflammation-based biomarkers and preventive strategies. In turn, Apolipoprotein E (APOE) polymorphism is the primary genetic risk factor for sporadic AD. The human form of the APOE gene possesses three polymorphic alleles: E2, E3, and E4, and the E4 allele occurs in 40% of AD patients. ApoE is a key regulator of lipid homeostasis and data is indicating that ApoE is associated with increased inflammatory responses before and after the onset of AD pathogenesis. In this regard, we propose to study the interplays between APOE genotype, blood inflammatory biomarkers, and inflammation-related gene polymorphisms in AD patients and cognitively healthy aged people. Our special focus of interest is studying the inflammation-related gene polymorphisms in APOE4 carriers with dementia in comparison with APOE4 carriers who are not demented. We hypothesize that APOE4 and some inflammation-related gene polymorphisms may exert synergistic effects significantly increasing the risks of AD. The proposed research will provide novel insights into how APOE and pro-inflammatory gene isoforms impact the risks of AD. This study can potentially contribute to the discovery of new genetic and blood-based biomarkers for earlier diagnosis of AD and give impetus to examine new therapeutic measures (e.g. CRISPR/Cas9 therapy) for the management/alleviation of AD-associated CNS outcomes.