Effects of single nucleotide polymorphisms (SNPs) on ADAM10 levels and activities in patients with dementia of Alzheimer's disease compared to cognitively healthy older adults

Abstract

Alzheimer's disease (AD) is a gradual and progressive neurodegenerative disease characterized by extensive neuronal loss and deposits of neurofibrillary tangles and senile plaques. ADAM10 is the main ±-secretase capable of acting on the non-amyloidogenic pathway of amyloid precursor protein (APP) cleavage and, therefore, preventing the formation of ²-amyloid peptide (A²), one of the pathological hallmarks of AD. Biomarkers that can diagnose AD in its early stages, preferably in samples that do not require highly invasive collection procedures, are the subject of many recent studies and represent a major clinical challenge in the area. Our group has been studying peripheral biomarkers for AD since 2010 with results indicating that ADAM10 levels are decreased in platelets and increased in plasma of elderly people with this dementia, compared to cognitively healthy elderly people. A recent longitudinal study showed that increased levels of plasma ADAM10 are able to predict participants' cognitive impairment at study follow-up, which was more pronounced in subjects who had normal mini-mental state examination (MMSE) scores at baseline, when compared with those with altered scores at baseline. Thus, the assessment of ADAM10 plasma levels in patients with suspected cognitive decline, but who have not yet achieved such decline, may allow for early interventions that could delay or even prevent AD. Single nucleotide polymorphisms of the gene that codes for ADAM10 have already been described and identified as risk factors for AD. However, studies on ADAM10 gene polymorphisms and their influence on the risk of AD are still scarce. In this sense, the objectives of this project to be developed by a postdoctoral researcher are to assess whether there are polymorphisms in the ADAM10 gene and whether such polymorphisms influence its levels and enzymatic activity in patients with AD compared to cognitively healthy participants.