Atividade e níveis da ADAM10 plasmática em indivíduos com transtorno neurocognitivo leve e doença de Alzheimer

Abstract

In dementias, alterations in brain functioning and progressive and global loss of cognitive functions are observed, interfering in the individual's social and occupational activities, with Alzheimer's disease (AD) being the main one. Mild neurocognitive impairment (MCI) can be considered a transient phase between normal cognition and AD and biomarkers that can diagnose these diseases in their early stages, preferably in samples that do not require highly invasive collection procedures, are the target of many recent studies and present a major clinical challenge in the area. AD is strongly related to the formation, accumulation and aggregation of the β-amyloid peptide (Aβ) in neurons. This molecule is formed by the sequential cleavage of β and γ-secretases, via a pathway called amyloidogenic. On the other hand, the sequential cleavage by α and γ-secretase, by the non-amyloidogenic pathway, prevents the formation of neuronal Aβ, and consequently, the appearance and advancement of AD. ADAM10 is the main neuronal α-secretase and is also present in platelets, white cells and CSF. Studies by our and other research groups indicate that the levels of active ADAM10 in platelets of patients with AD are decreased compared to healthy subjects. Thus, ADAM10 is a strong candidate for blood biomarkers for AD. In this sense, this study aims to evaluate the levels and activity of ADAM10 in the blood plasma of subjects with AD and MCI, in order to support the function of this protein as a biomarker for these conditions. Previous results from our group allowed us to elaborate the hypothesis of this study that the levels of soluble and therefore possibly inactive ADAM10 in the plasma of subjects with MCI and AD would be increased, compared to the levels of cognitively healthy subjects.