UCSF scientists have discovered how microglia engulfs and decomposes the beta amyloid, a protein that accumulates in Alzheimer, with devastating consequences for the brain.
In Alzheimer’s disease, proteins like the beta amyloid form tufts, called plates, which damage the brain.
But in some people, immune cells called microglies decompose these proteins before they can harm. This leads to less and smaller tufts – and much softer symptoms.
UC San Francisco researchers have identified a molecular receptor that allows microglies to engulf and digest amyloid beta plates.
Without the receiver, ADGRG1, microglia has barely nibbled the toxic protein. Using a mouse model of Alzheimer’s disease, researchers observed how the loss of ADGRG1 led to the rapid accumulation of amyloid plates, neurodegeneration and learning and memory problems.
“We believe that this receiver helps microglia do its job to keep the brain healthy for many years. »»
Xianhua Piao, MD, PHD, doctor-scientist, department of pediatrics, University of California-San Francisco
Indeed, when the researchers reanalyzed an earlier study of the expression of genes in the human brain, they found that the deceased individuals of a light Alzheimer had a microglia with an abundant adgrg1, and a slight cognitive impairment – which implies that microglia has eaten well and kept the disease in control. But in those who died of a severe Alzheimer’s, microglia had very little Adgrg1 and the plates proliferated.
ADGRG1 is one of the hundreds of receptors coupled with G proteins, which are systematically targeted in the development of drugs. This augurs well for a quick translation of discovery into new therapies.
“Some people are fortunate to have responsible microglies,” said Piao. “But this discovery creates an opportunity to develop medication to make microglia effective against the amyloid-bêta throughout the world. »»