Clinical Research Directory

Marker of Brain Insulin Resistance in AD Prognosis

Basic research data from the literature on the links between cerebral insulin resistance and Alzheimer's disease (AD) suggest that this pathophysiological mechanism is involved at a very early stage in the development of the disease. The insulin receptor (IR) is a tyrosine kinase receptor whose activation by insulin binding leads to autophosphorylation of its IRβ subunits and then of the insulin receptor substrate proteins (IRS-1). The ratio of IRS residues phosphorylated on serine 312 (P(Ser312)-IRS-1) to total phosphorylated IRS or IRS phosphorylated on its tyrosines has been proposed by some authors as an index of insulin resistance in the brain. IRS-1 proteins can be measured in exosomes, and in particular in neuronal exosomes isolated from plasma. It is therefore conceivable to measure this index in these biological samples specifically derived from neurons and available from a simple blood test, in order to determine whether it could be of prognostic interest in patients with mild cognitive impairment (MCI), in particular by making it possible to identify at an early stage patients who are going to convert to AD.