Micropartículas, citocinas e leptina: possíveis biomarcadores do comprometimento cognitivo no envelhecimento?

Abstract

The clinical impairment established on Alzheimer’s Disease (AD) compromises the cognitive fuction, accompanied by personality and behavioral changes. On Mild Cognitive Impairment (MCI), the daily activities are preserved. In Subjective Cognitive Decline (SCD), there is a self-perceived decline, but without evidence of cognitive decline on standard neuropsychological tests. However, this condition may precede frequently the MCI and AD. Microparticles (MPs) are associated to cellular activation during inflammation, coagulation, vascular injuries and homeostasis. An inflammatory process is part of AD pathophysiology. And leptin has been demonstrated to have a neuroprotective role against AD pathology. This study aimed to investigate the MPs and cytokines levels, IL-1β, IL-6, TNF-α and IL-10; leptin and high sensitivity C Reactive protein (hsCRP) levels on patients with cognitive impairment (AD and MCI) and subjects with no objective cognitive impairment (SCD and controls). We evaluated platelets-derived MPs (PMPs), leukocytes-derived MPs (LMPs), tissue factor-derived MPs (TFMPs), endothelium-derived MPs (EMPs) and neuron-derived MPs (NMPs) levels in plasma, by flow cytometer assay. The cytokines and leptin levels were determined using enzyme linked immunosorbent assay (ELISA). And the hsCRP levels by immunoturbidimetric assay. We observed that TFMPs, LMPs and NMPs levels were significant increased, and IL-6, IL-1β, TNF-α and hsCRP were found to be significant lower in the AD group when compared to controls. The multiple logistic regression showed that TNF-α and NMPs were independently associated to AD, which resulted in a ROC curve with an area under the curve of 0.957 (sensitivity = 100% and specificity = 70%). Moreover we found higher MPs levels in sbjects with functional cognitive impairment and lower IL-6, IL1β, TNF-α and hsRCP and the functional and cognitive impairment, and lower levels of TNFα in subjects with no cognitive impairment. We found no difference in leptin levels between the cognitive impairment groups and SCD group. However, women demonstrated higher leptin serum levels than men. Higher leptin levels were observed in individuals ≥ 79 years old. The results suggest that MPs and TNF-α have a promising potential as biomarkers for AD diagnosis, but that leptin levels is not involved in the evolution for the cognitive impairment state but it is associated with inflammation, sex and age.