A Mechanism By Which Amyloid-β Attacks Synapses

Researchers here provide evidence for a fairly direct link between the growing levels of amyloid-β associated with Alzheimer's disease and the loss of synapses characteristic of the condition. Since the mechanism is so direct, success in present efforts to clear amyloid-β from the brain, such as via immunotherapy, should also minimize this part of the pathology of Alzheimer's disease:

"One of the first signs of Alzheimer's disease is the loss of synapses - the structures that connect neurons in the brain. Synapses are required for all brain functions, and particularly for learning and forming memories. In Alzheimer's disease, this loss of synapses occurs very early on, when people still only have mild cognitive impairment, and long before the nerve cells themselves die. We have identified a new molecular mechanism which directly contributes to this synapse loss - a discovery we hope could eventually lead to earlier diagnosis of the disease and new treatments."

The team studied a protein in the brain called neural cell adhesion molecule 2, or NCAM2 - one of a family of molecules that physically connects the membranes of synapses and help stabilise these long lasting synaptic contacts between neurons. Using post-mortem brain tissue from people with and without the condition, they discovered that synaptic NCAM2 levels in the part of the brain known as the hippocampus were low in those with Alzheimer's disease. They also showed in mice studies and in the laboratory that NCAM2 was broken down by another protein called beta-amyloid, which is the main component of the plaques that build up in the brains of people with the disease. "Our research shows the loss of synapses is linked to the loss of NCAM2 as a result of the toxic effects of beta-amyloid. It opens up a new avenue for research on possible treatments that can prevent the destruction of NCAM2 in the brain."

Link: http://www.eurekalert.org/pub_releases/2015-11/uons-sdc112415.php

Comments

GAIM technology by Neurophage is a very promising drug and on it's second improved candidate thanks to support by Michael J Fox foundation. This clears multiple amyloids and a friend of mine who is an AD researcher but not involved with the project says it is very promising indeed.

Posted by: Steve H at November 27th, 2015 6:44 AM

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