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Alzheimer's Disease Brain and Mental Performance Healthcare and Information Immune System

Neurogenesis Can Be Disrupted By The Brain’s Own Immune Cells

1 year, 11 months ago

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Posted on Sep 03, 2019, 12 p.m.

Much of Alzheimer’s research focuses on accumulation of amyloid beta protein that form clumps/plaques which disrupts communication between brain cells and triggers inflammation eventually leading to loss of neurons and brain tissue.

As published in the Journal of Neuroscience, neuroscientists from the University of Chicago are investigating another process which may play a role in progression of AD: neurogenesis; the process of creating new brain cells, which can be disrupted by the brain’s own immune cells.

Some types of early onset are caused by mutation in PS2 and PS2. Animal studies have shown healthy mice placed into enriched environments where they can interact, play, and exercise with each other have significant increases in new brain cells created in the hippocampus. Mice carrying the mutations placed in the enriched environment don’t display the same increase, and often start to display signs of anxiety which is a symptom often reported by those with early onset. This caused the team to wonder what else besides genetics may be involved, and the suspicion of neurogenesis possibly being influenced by other cells that interact with the newly forming brain cells.

Focusing on microglia immune cells that repair synapses, the team gave the mice a drug that causes microglial cells to die which resulted in neurogenesis returning to normal; then animals with presenilin mutations were placed into the enriched environment and were not observed to display any signs of anxiety or memory deficits, and they were creating a normal amount of new neurons. 

"It's the most astounding result to me," Sisodia said. "Once you wipe out the microglia, all these deficits that you see in these mice with the mutations are completely restored. You get rid of one cell type, and everything is back to normal."

It is thought that microglia may be overplaying their roles in the immune system: Alzheimer’s disease causes inflammation in the microglia, when they interact with newly formed cells with mutations they may be overreacting and killing them off prematurely, according to Sisodia. 

“I've been studying amyloid for 30 years, but there's something else going on here, and the role of neurogenesis is really underappreciated," he said. "This is another way to understand the biology of these genes that we know significantly affect the progression of disease and loss of memory."

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