Deciphering the microglia-neuron interactions in human Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease and is the most common form of dementia. AD is characterized by the build-up of abnormal protein, in the form of amyloid beta plaques and tau tangles. AD is accompanied by changes in the immune cells of the brain, the microglia. This inflammation in the brain is referred to as neuroinflammation. Recent genetic studies revealed a link between neuroinflammation and susceptibility to develop AD. This suggests that inflammation might be a driver of the disease opposed to just a consequence of the neuronal loss. One of the main forms by which microglia may contribute to AD is by destroying the connections between neural cells, called synapses. However, the specific cellular and molecular players that mediate this noxious interaction between microglia and synapses are poorly understood. We have generated novel models of AD where human derived cells are injected into AD mice, in order to expose those cells to the environment they would find in the pathological brain. We propose to use these models to dissect the exact molecular pathways that negatively impact the human brain. These findings would have major implications for our understanding of the progression of human AD and would allow tailored treatments to slow down or arrest AD progression. This is an approach that addresses a critical component of the pathology in the AD brain and has the potential to change the disease trajectory and patients' quality of life.

Keywords:MICROGLIA, NEUROINFLAMMATION, ALZHEIMER'S DISEASE

Disciplines:Neurological and neuromuscular diseases