Study of the genetic variants in the microglial CX3CR1, KATP and NADPH oxidase genes as risk factors for neurodegenerative diseases: Alzheimer disease and Lateral Amiotrophic Sclerosis

The activated microglia (the resident macrophage of the CNS) is present in a high number of patients with chronic neurodenerative diseases, including Alzheimer disease (AD) and Lateral Amiotrophic Sclerosis (ALS). It has been proposed that the activated microglia is a factor that contributes to the chronic neurodegeneration of the AD. In ALS, the microglia cells are activated surrounding the degenerating zone of the neuromotor cells. There are a group of genes expressed in microglia cells (NADPH oxidase, TNFα, NOS2, …) that they have been associated with the activation of these cells when the brain is injured or when these cells are stimulated by some infection signals such as LPS and interferon. The CX3CR1 gene (a chemokine receptor) is critical in the microglia-neuron communication, and in animal models for AD, the no expression of this gene protects against the neuronal death. CX3CR1 polymorphisms have been associated to the susceptibility to suffer the Crohn inflammatory disease. The NADPH oxidase and the K-ATP channel genes are fundamental in the microglial activation and their neurotoxic and neurodegenerative phenotype. There are functional polymorphisms in the NADPH oxidase and the K-ATP channel genes associated to several diseases, but neither the functional implications nor the relationship with the risk of developing AD or ALS have not been studied in microglia
In this project we would carry out a genetic association study of the NADPH oxidase, CX3CR1 and K-ATP genes and the risk and severity of suffer AD or ALS.