Research Highlights - October 2018

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Now, let’s examine the most important technological and scientific breakthroughs emerging from labs around the world.

Beta-amyloid protein attacks and destroys synapses, the connections between nerve cells in the brain.  This results in memory problems, dementia and ultimately death. Overproduction of beta-amyloid is strongly linked to development of Alzheimer’s disease, but many drugs targeting beta-amyloid have failed in clinical trials.

Researchers at King’s College London have discovered a vicious “feedback loop” underlying brain degeneration in Alzheimer’s disease; this loop seems to explain why so many drug trials have failed.  The study also identifies a clinically approved drug which breaks the vicious cycle and protects against memory-loss in animal models of Alzheimer’s.

In the new study, published in the journal, Translational Psychiatry, researchers found that when beta-amyloid destroys a synapse, the nerve cells make more beta-amyloid driving yet more synapses to be destroyed.  The result is that a vicious positive feedback loop exists in which beta-amyloid drives its own production.  Once this feedback loop gets out of control it is too late for drugs which target beta-amyloid to be effective, and this could explain why so many Alzheimer’s drug trials have failed.

This work highlights the intimate link between synapse loss and beta-amyloid in the earliest stages of Alzheimer’s disease and the importance of early therapeutic intervention.”

The researchers also confirmed that a protein called Dkk1, potently stimulates production of beta-amyloid and is central to the positive feedback loop. Dkk1 is a key player in Alzheimer’s. And while it is barely detectable in the brains of young adults, its production increases as we age.

Instead of targeting beta-amyloid itself, the researchers believe targeting Dkk1 could be a better way to halt the progress of Alzheimer’s disease by disrupting the vicious cycle of beta-amyloid production and synapse loss.

Importantly, this work has shown that we may already be in a position to block the feedback loop with a drug called fasudilwhich is already used in Japan and China for stroke treatment.  The new research has...

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