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Revealed: how Alzheimer's infects the brain

Breakthrough may lead to new treatments for senile dementia

By Steve Connor, Science Editor

A scientific breakthrough in the understanding of how Alzheimer's disease may spread across the brain of elderly patients might lead to novel ways of treating senile dementia, scientists have announced.

A study has discovered that a key brain protein linked with Alzheimer's disease has infectious properties that allow defects in the protein to be transmitted through the brain and so leads to debilitating neuro-degeneration.

It is the first time that scientists have detected infectious properties in the so-called tau protein which causes aggregates of particles known as "neurofibrillary tangles" to build up inside the brain cells of Alzheimer's patients. The tangles lead to the disease's symptoms.

But the researchers emphasised that the discovery does not mean that the disease itself is infectious, only that the tau protein seen in Alzheimer's disease is able to convert otherwise healthy brain proteins into the defective form associated with the disease.

Alzheimer's disease is one of the fastest growing and most costly medical conditions. About 700,000 people in the UK have some form of dementia and this will grow to about 940,000 by 2015, rising to more than 1.7 million by 2051 as a result of the demographic time bomb of an ageing population.

Medical researchers believe that the latest findings – which have so far been shown in laboratory mice rather than human patients – could open up new ways of treating Alzheimer's disease by developing drugs that block the tau's infectious properties.

The results of the study also show that Alzheimer's disease has underlying similarities to Creutzfeldt-Jakob disease (CJD), a brain disease that is believed to be caused by other kinds of infectious proteins called "prions" which can, under certain circumstances, be transmitted from one person to another.

Scientists have known for many years that the brain cells of Alzheimer's patients experience a build up of tau protein in the form of complicated tangles and that these tangles spread in a characteristic fashion through the brain.

The latest study, published in the journal Nature Cell Biology, offers the first proper explanation for how these tangles spread and suggests a possible target for drug companies hoping to develop ways of slowing down the progression of Alzheimer's disease.

"This opens new avenues in dementia research that will aim to understand how abnormal tau can spread. We can also investigate how diseases caused by tau aggregates and prions are similar," said Michel Goedert of the Medical Research Council's Laboratory of Molecular Biology in Cambridge.

"We have looked at whether tau tangles can spread in mice. The injection of brain extract from tangle-bearing mice into animals without tangles caused their tau to tangle and spread from the sites of injection to neighbouring brain regions," said Dr Goedert, who took part in the study.

The scientists used a strain of genetically modified mouse with a gene for the human form of the defective tau protein. When the tau of this mouse was injected into the brain of ordinary laboratory mice, it caused a build-up of the same sort of tangles seen in Alzheimer's patients.

"This research in mice does not show that tau pathology is contagious or that it can spread easily from mouse to mouse. What it has revealed is how tau tangles spread within brain tissues of individual mice," Dr Goedert said.

"It suggests that tangles of proteins that build up in the brain to cause symptoms could have some contagious properties, within brain tissue but not between mice that haven't been injected with tissue from another mouse and certainly not between people," he said.

There is no epidemiological evidence that brain diseases like Alzheimer's or Parkinson's can spread from one person to another and the latest study does not suggest that such disorders are caused by an infection, said David Allsop, professor of neuroscience at Lancaster University.

"This is interesting because it could explain how tangles spread from one region of the brain to another during the course of Alzheimer's disease and some other 'tangle' diseases," Professor Allsop said.

Susanne Sorensen, the head of research at the Alzheimer's Society, said that the study could result in a greater understanding of how tau tangles form and spread through the brain.

"There is still so much we do not understand about the changes in tau that lead to tangle formation in humans and, eventually, widespread cell death," Dr Sorensen said. "Each new piece of knowledge helps to build a better picture and takes us closer to the point where we can stop loss of brain tissue and dementia for good."

Rebecca Wood, the chief executive of the Alzheimer's Research Trust, said: "This greater understanding of how tangles spread in Alzheimer's may lead to new ways of stopping them and defeating the disease."

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Comments

Treatment for Dementia
[info]redroseandy wrote:
Monday, 8 June 2009 at 04:06 am (UTC)
The Kadir-Buxton Method is a known treatment for dementia, and takes just thirty seconds for the patient to get back to normality.
Prions - it's rubbish
[info]old_green wrote:
Monday, 8 June 2009 at 08:29 am (UTC)
Microbiologist Harash Narang revealed in the 80s that nvCJD was caused by a virus infection.
The virus causes the growth of tubercles inside the nerve fibres, structures which become coated with prions. The prions are not the primary cause of the infection or tubercle growth.

Narang showed that this was a special type of virus - single-strand and that its DNA was repeating and pallindromic 9i.e. is the same read in either direction). This makes it incredibly easy for the DNA to repair itself, if damaged, thus very hard to kill the virus. Basically, it is very easy for matching sections of DNA to align and splice together. This is, in fact, how the virus fibres grow.

This article shows that there may be certain similarities between Alzheimer's and nvCJD, in terms of a tubercle growth inside the nerves in brain tissue. Very worrying.
Drug that target Tau tangles in clinical trials
[info]paulbrowne wrote:
Tuesday, 9 June 2009 at 11:00 am (UTC)
It's worth noting that a drug called Rember that targets the tau tangles has performed well in Phase II clinical trials, following promising results in earlier animal studies. It will probably be another 3-4 years, assuming that larger Phase III trials go well, before Rember is licenced for widespread use.

http://www.guardian.co.uk/science/2008/jul/30/medicalresearch.health

Doubtless this latest discovery will spur further research to develop even more effective drugs.
Alzheimer's Caregiver
[info]knowitalz wrote:
Sunday, 14 June 2009 at 01:54 am (UTC)
My name is Kathy and I am 39. I am the full time caregiver to my Dad who has Alzheimer's and lives with me.

In addition to caring for Dad, I have a full time job, 3 dogs, my love of 12 years David and his 14 year old daughter. I get overwhelmed a lot but try to find the humor if I can.

I am writing a blog which shows the lighter side of caring for someone with dementia.

www.KnowItAlz.com

Please pass this link along to anyone you feel would enjoy it.

Thanks!
Kathy

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