What is it about?
The most widely accepted model for Alzheimer's Disease for the last 20 years in the Amyloid Cascade Hypothesis, where over-production of beta-amyloid leads to a series of steps culminating in the death of brain cells and hence dementia. Here, I show that there is much evidence for feedback loops, where steps in the processes feedback to give vicious cycles that commit the brain to Alzheimer's.
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Why is it important?
The feedback loop model implies that we should take more seriously a wider range Alzheimer's processes as drug targets, such as oxidative stress and inflammation. It may also be necessary to hit multiple targets at the same time, rather than just one.
Perspectives
I was driven to write this review after reading numerous examples of feedback processes in Alzheimer's. This meant that the disease cannot be a cascade, since a cascade is a series of waterfalls, and water cannot flow uphill. I thought it was important to point out that there is excellent evidence for feedback loops and what this means for drug discovery for this important disease.
Prof. Andrew Doig
University of Manchester
Read the Original
This page is a summary of: Positive Feedback Loops in Alzheimer’s Disease: The Alzheimer’s Feedback Hypothesis, Journal of Alzheimer’s Disease, October 2018, IOS Press,
DOI: 10.3233/jad-180583.
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