The brain deterioration caused by Alzheimer’s Disease (AD) is one of the largest challenges facing medical science today. Postmortem analyses of the brains of people who had died of AD have found two substances not found in normal brains, amyloid-beta plaques and tau tangles.

The thinking of researchers has been that perhaps these plaques and tangles are causing the disease, and if they could be eliminated, the progression of the disease could be slowed or even stopped. This idea makes sense, but one trial after another, that targeted the amyloid beta plaques in test subjects, has failed.

A new way of looking at the problem, by researchers at the University of Alabama at Birmingham (UAB), has shed some much needed light on how amyloid beta plaques and tau tangles could be causing disease, and on why previous attempts to treat the disease by eliminating them have failed. The key insight involves the mechanism by which amyloid beta and tau work together to cause disease.

Amyloid beta by itself is not enough to cause AD. People who died of other causes and were cognitively intact, have had brains that were festooned with amyloid beta plaques. Similarly, tau tangles by themselves do not guarantee a diagnosis of AD either. However, when both are present, disease ensues. It has been known that somehow amyloid beta plaques trigger tau tangles to attack neurons, but the mechanism for this has been unclear.

The UAB team has determined that amyloid-beta oligomers hijack normal norepinephrine signaling at brain neurons, which then go on to activate the GSK3-beta kinase, an enzyme that hyper-phosphorylates tau protein, making it toxic.

An existing drug, idazoxan, currently undergoing clinical trials for depression, blocks the receptor that enables the hyperactivation of GSK3-beta in the brains of mice that have a mouse version of AD. After an eight-week course of treatment with idazoxan, the treated mice performed almost as well on cognitive tasks as normal disease-free controls and much better than untreated AD mice.

Because idazoxan is an already existing drug, it should be possible to move to clinical trials in humans much sooner that would be possible with a new drug that has not already jumped through the hoops of approval for use in humans. Also, since the path that leads to the triggering of AD has now been elucidated, other drugs that would derail that path can be investigated, and perhaps perform even better than idazoxan. It appears that there may be light in the distance at the end of a very long and horrific tunnel.

BIO:

Allen G. Taylor is a 40-year veteran of the computer industry and the author of over 40 books, including Develop Microsoft HoloLens Apps Now, Get Fit with Apple Watch, Cruise for Free, SQL For Dummies, 9thEdition, Crystal Reports 2008 For Dummies, Database Development For Dummies, Access Power Programming with VBA, and SQL All-In-One For Dummies, Third Edition. He lectures internationally on astronomy, databases, innovation, and entrepreneurship. He also teaches database development and Crystal Reports through a leading online education provider. For the latest news on Allen’s activities, check out his blog at wwwallengtaylor.com or contact him at allen.taylor@ieee.org.