Comparative Characteristics of Inflammatory Markers in Alzheimer’s Disease in Males and Females

Abstract

Background: the role of the sex factor in the differences between the manifestations of normality and pathology is not limited to the phenomenon of sexual dimorphism. It is known that the prevalence of certain diseases in males and females is different, in particular, there is a multiple increase in the incidence of dementia in females compared to males in Alzheimer’s disease (AD). Taking into account the role of neuroinflammation in the pathogenesis of neurodegenerative diseases, there is reason to assume gender differences in inflammation indicators at different stages of dementia in AD. The aim of the study was to conduct comparative analysis of indicators of the inflammatory system in the blood plasma of males and females at different stages of Alzheimer’s disease. Patients, control group and methods: a total of 210 patients with AD (101 males and 109 females) aged 49 to 94 years (average age 72.3 ± 8.2) with varying degrees of dementia severity, i.e. mild, moderate, severe, were examined. In peripheral blood plasma, the enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI) were determined by the spectrophotometric method, and the level of C-reactive protein (CRP) and IL-6 were determined by the enzyme-linked immunosorbent method (ELISA). The control group consisted of 52 healthy people, who did not differ from the patients in age and gender. Results and discussion: in the blood of patients with varying severity of dementia in AD, a statistically significant increase in α1-PI activity was observed compared to controls (p < 0.0001), regardless of gender. For all subgroups of patients with AD, the indicators of LE enzymatic activity were within the control range or beyond its lower limit. Low LE activity was observed in males compared to females both in the general group and in moderate dementia (p = 0.005105, p = 0.028672, respectively). In severe dementia, a significant decrease in LE activity compared to the controls did not depend on gender. Low LE activity in the blood of patients with AD, along with elevated levels of other inflammatory markers, may reflect a critical violation of the permeability of the blood-brain barrier and/or functional exhaustion of neutrophils due to a long-term inflammatory process. In males, compared with females, an increase in the level of the pro-inflammatory cytokine IL-6 was detected in the general group and in moderate dementia (p = 0.021238, p = 0.027894, respectively). A highly significant increase in CRP levels was only detected in males in subgroups with different severity of dementia. CRP levels in males were significantly higher than in females at the stage of moderate and severe dementia (p = 0.000906, p = 0.000049, respectively). Conclusion: distinctive features of inflammatory markers spectrum were identified, depending on gender and severity of dementia in AD. These results can be used to develop sex-specific preventive or therapeutic strategies for patients with mild cognitive impairment to determine risk and resistance to developing dementia.