Vesicles, fluid-filled sacs that brain cells make to trap amyloid, a hallmark of Alzheimer's, appear to also contribute to the disease, scientists report. Reducing the production of these vesicles, called exosomes, could help reduce the amount of amyloid and lipid that accumulates, slow disease progression, and help protect cognition, scientists at the Medical College of Georgia (MCG) at Augusta University reported in the August 17, 2016 issue of The Journal of Neuroscience. The article is titled “Neutral Sphingomyelinase-2 Deficiency Ameliorates Alzheimer's Disease Pathology and Improves Cognition in the 5XFAD Mouse.” When confronted with amyloid, astrocytes (plentiful brain cells that support neurons) start making exosomes, to capture and neutralize it, said Dr. Erhard Bieberich, a neuroscientist in the MCG Department of Neuroscience and Regenerative Medicine and the study's corresponding author. "If you swarm astrocytes with amyloid, you trigger an aggressive response," he said. Happy astrocytes, on the other hand, don't make exosomes. Not unlike a landfill, the real problems begin when the biological sacs get piled too high. In such volume and close proximity to neurons, exosomes begin to interfere with communication and nutrition, neurons stop functioning well and eventually begin to die, a scenario that fits with disease progression, Dr. Bieberich said. MCG scientists followed the process in an animal model with several genetic mutations found in types of Alzheimer's that tend to run in families and produce brain plaques early in life. One mouse group also was genetically programmed to make a nonfunctional form of the enzyme neutral sphingomyelinase-2.
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