Untangling the mysteries of Alzheimer's

February 2, 2012

One of the most distinctive signs of the development of Alzheimer's disease is a change in the behavior of a protein that neuroscientists call tau. In normal brains, tau is present in individual units essential to neuron health. In the cells of Alzheimer's brains, by contrast, tau proteins aggregate into twisted structures known as "neurofibrillary tangles." These tangles are considered a hallmark of the disease, but their precise role in Alzheimer's pathology has long been a point of contention among researchers.

Now, University of Texas Medical Branch at Galveston researchers have found new evidence that confirms the significance of tau to Alzheimer's. Instead of focusing on tangles, however, their work highlights the intermediary steps between a single unit and a neurofibrillary tangle — assemblages of two, three, four, or more tau proteins known as "oligomers," which they believe are the most toxic entities in Alzheimer's.

"What we discovered is that there are smaller structures that form before the neurofibrillary , and they are much more toxic than the big structures," said Rakez Kayed, UTMB assistant professor and senior author of a paper on the work now online in the FASEB Journal. "And we established that they were toxic in real human brains, which is important to developing an effective therapy."

According to Kayed, a key antibody developed at UTMB called T22 enabled the team to produce a detailed portrait of tau oligomer behavior in human tissue. Specifically designed to bond only to tau oligomers (and not lone tau proteins or ), the antibody made it possible for the researchers to use a variety of analytical tools to compare samples of Alzheimer's brain with samples of age-matched healthy brain.

"One thing that's remarkable about this research is that before we developed this antibody, people couldn't even see tau oligomers in the brain," Kayed said. "With T22, we were able to thoroughly characterize them, and also study them in human brain cells."

Among the researchers' most striking findings: in some of the Alzheimer's brains they examined, tau oligomer levels were as much as four times as high as those found in age-matched control brains.

Other experiments revealed specific biochemical behavior and structures taken on by oligomers, and demonstrated their presence outside — in particular, on the walls of blood vessels.

"We think this is going to make a big impact scientifically, because it opens up a lot of new areas to study," Kayed said. "It also relates to our main focus, developing a cure for Alzheimer's. And I find that very, very exciting."

Explore further: Alzheimer's protein detected in brain fluid of healthy mice

Related Stories

Alzheimer's protein detected in brain fluid of healthy mice

September 21, 2011

(Medical Xpress) -- One of the most promising markers of Alzheimer’s disease, previously thought only to be inside nerve cells, now appears to be normally released from nerve cells throughout life, according to researchers ...

Alzheimer's vaccine cures memory of mice

December 9, 2011

(Medical Xpress) -- A vaccine that slows the progression of Alzheimer's disease and other types of dementia has been developed by researchers at the University of Sydney's Brain and Mind Research Institute (BMRI).

Recommended for you

How even our brains get 'slacker' as we age

October 24, 2016

New research from Newcastle University, UK, in collaboration with the Federal University of Rio de Janeiro, investigated the way the human brain folds and how this 'cortical folding' changes with age.

How lying takes our brains down a 'slippery slope'

October 24, 2016

Telling small lies desensitises our brains to the associated negative emotions and may encourage us to tell bigger lies in future, reveals new UCL research funded by Wellcome and the Center for Advanced Hindsight.

Robotic tutors for primary school children

October 24, 2016

The use of robotic tutors in primary school classrooms is one step closer according to research recently published in the open access journal Frontiers in Computational Neuroscience.

Mouse decision-making more complex than once thought

October 24, 2016

Working with dot-counting mice running through a virtual-reality maze, scientists from Harvard Medical School have found that in order to navigate space rodent brains rely on a cascade of neural signals that culminate in ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Feb 02, 2012
I presume the analysis was carried out via autopsy?, is it possible to do this in vivo?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.