The INFLUENCE OF THE APOEε4 ALLELE ON PRO-INFLAMMATORY CYTOKINE LEVELS IN THE CEREBROSPINAL FLUID OF PATIENTS WITH ALZHEIMER’S DISEASE

Abstract

Single nucleotide polymorphisms (SNPs) rs429358 and rs7412, the most commonly investigated variants in the apolipoprotein E gene (APOE) are crucial for APOEε4 carrier status determination. However, their association with inflammatory cytokine levels in patients with dementia due to Alzheimer’s disease (AD) remains unclear. This study aimed to investigate the influence of the APOEε4 allele on pro-inflammatory cytokine levels in the cerebrospinal fluid of patients with AD dementia. The research was conducted on 36 patients with probable dementia due to AD. APOE rs429358 and rs7412 were analyzed using the Real-Time PCR method with allele-specific TaqMan assays, followed by the analysis of APOEε4 allele carrier status. Patients carrying at least one APOEε4 allele were assigned as APOEε4+. Core biomarkers (Aβ42/40 ratio, t-Tau, p-Tau levels), as well as pro-inflammatory cytokine (Tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b)) levels, were determined in the patient’s cerebrospinal fluid (CSF) using Enzyme-linked Immunosorbent Assay (ELISA). Seventeen patients (47.22%) were assigned as APOEε4+. CSF TNF-α levels were significantly higher in APOEε4+ AD dementia patients in comparison to APOEε4- patients (p<0.001), while no significant differences in IL-1b levels between these two groups were obtained. Correlation analysis showed that TNF-α negatively correlated with the Aβ42/40 ratio (p=0.033), while positive correlation with t-Tau and p-Tau was observed (p=0.001, p=0.015, respectively). These findings highlight the potential significance of TNF-α in the context of APOEε4 positivity and its implications in AD pathology.

Matrix Remodeling Enzymes as Potential Fluid Biomarkers of Neurodegeneration in Alzheimer’s Disease

“…In our previous research, the APOE ε4 allele has been linked to increased levels of TNF-α [ 15 ] and IL-1β [ 38 ], as well as compromised BBB integrity [ 39 ] and dysfunction of tight junctions [ 40 ]. Pericytes and MMP-9 have been proposed as potential mediators of these effects [ 26 ].…”

“…The APOE ε4 allele is known to be a significant genetic risk factor for AD, and its presence can influence the levels of various inflammation-related biomarkers [ 3 , 14 , 15 ]. Research into the interrelation between APOE ε4 carrier status, plasma biomarkers, and hippocampal volume is crucial, as hippocampal atrophy is a well-established indicator of AD.…”