Untangling the mysteries of Alzheimer's

February 2, 2012, University of Texas Medical Branch at Galveston

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 ...

Chemical engineers help decipher mystery of neurofibrillary tangle formation in Alzheimer's brains

November 2, 2011
Neurofibrillary tangles – odd, twisted clumps of protein found within nerve cells – are a pathological hallmark of Alzheimer's disease. The tangles, which were first identified in the early 1900s by German psychiatrist ...

Study shows Alzheimer's disease may spread by 'jumping' from one brain region to another

February 1, 2012
For decades, researchers have debated whether Alzheimer's disease starts independently in vulnerable brain regions at different times, or if it begins in one region and then spreads to neuroanatomically connected areas. A ...

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

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

How your brain remembers what you had for dinner last night

January 17, 2018
Confirming earlier computational models, researchers at University of California San Diego and UC San Diego School of Medicine, with colleagues in Arizona and Louisiana, report that episodic memories are encoded in the hippocampus ...

Recording a thought's fleeting trip through the brain

January 17, 2018
University of California, Berkeley neuroscientists have tracked the progress of a thought through the brain, showing clearly how the prefrontal cortex at the front of the brain coordinates activity to help us act in response ...

Midbrain 'start neurons' control whether we walk or run

January 17, 2018
Locomotion comprises the most fundamental movements we perform. It is a complex sequence from initiating the first step, to stopping when we reach our goal. At the same time, locomotion is executed at different speeds to ...

Miles Davis is not Mozart: The brains of jazz and classical pianists work differently

January 16, 2018
Keith Jarret, world-famous jazz pianist, once answered in an interview when asked if he would ever be interested in doing a concert where he would play both jazz and classical music: "No, that's hilarious. [...] It's like ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

gmurphy
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.