Monday, February 18, 2013

Rare gene mutation offers clues to Alzheimer's

Posted: 16 November 2012

Looking at a specimen
WASHINGTON: Scientists have found a rare genetic mutation that appears to triple the risk for developing Alzheimer's disease and provides important clues into how the so-far incurable disease operates.

Scientists from two independent teams stumbled on the same result, published in two studies Wednesday in the New England Journal of Medicine: a mutation in the TREM2 gene, which helps govern immune system responses, is three to four times more common among elderly patients with Alzheimer's than those without the diagnosis.

The hallmark of Alzheimer's disease is the accumulation of plaques and tangles in the brain tissue. In normal bodies, it seems the immune system's inflammatory molecules help clear that build-up before it becomes a problem.

The TREM2 gene functions to keep that inflammatory response in check, to stop the inflammatory molecules from harming healthy tissue.

But preliminary research indicates the mutation could send the TREM2 gene into overdrive, hindering the inflammatory molecules from doing their job at all.

"While the genetic mutation we found is extremely rare, its effect on the immune system is a strong indicator that this system may be a key player in the disease," said University College London's Rita Guerreiro, lead author of one of the two studies.

The mutation is found in fewer than one in 200 people, and in fewer than one in 50 Alzheimer's patients, which means the mutation alone is unlikely to be enough to cause the disease.

A combination of environmental and hereditary factors is believed to contribute to developing Alzheimer's.

However, researchers said identifying this gene and its possible role in Alzheimer's is a step in the right direction.

"This is an important step towards unravelling the hidden causes of this disease, so that we can develop treatments and interventions to end one of the 21st century's most significant health challenges," said Peter St. George-Hyslop, of the University of Toronto.

Another of the lead researchers, Kevin Morgan of the University of Nottingham, said "the risk associated with this new variant is the largest seen to date and heralds the start of a new era in (Alzheimer's disease) genetic research.

"At long last we are beginning to witness major breakthroughs that will hopefully result in therapeutic developments to help alleviate this devastating condition."

The scientists said that new drugs could potentially be developed to target the TREM2 gene and stop it from overly interfering in the inflammatory response.

One of the studies was done by an international research team based in Britain, Canada and the US, using a data bank of 25,000 people.

The other was done by researchers in Iceland, using data from 2,261 elderly Icelanders and then confirmed with population samples in the US, Norway, the Netherlands and Germany.


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Rare gene mutation offers clues to Alzheimer's

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Friday, January 25, 2013

Alzheimer's may be detectable earlier than thought

Another article on Alzheimer's...

Posted: 06 November 2012

A woman, suffering from Alzheimer's desease, walks along a corridor in a retirement home. (AFP/Sebastien Bozon)
PARIS: Researchers said Tuesday they had seen the earliest-ever warning signs of Alzheimer's Disease -- among a high-risk group of 20-somethings -- in the ongoing quest for early detection and prevention.

A major problem in the search for a cure for this debilitating form of dementia is that symptoms appear years after irreversible brain decay has already set in.

For the study, a team of scientists from the United States and Colombia tested 18- to 26-year-old members of an extended Colombian family that share a common ancestor and a genetic predisposition to develop an inherited form of Alzheimer's.

One in three members of the clan carry a gene mutation that will lead to a rare form of the disease which hits people in their 40s, unlike the common variant which presents much later.

A brain scan comparison found that individuals who carry the errant gene have less grey matter in certain areas of the brain than those who don't, scientists wrote in The Lancet medical journal.

They also found that those with the mutation had higher levels in their cerebrospinal fluid of a protein called amyloid beta, implicated in the plaque build-ups found on the brains of Alzheimer's sufferers.

The findings "suggest that neurodegenerative changes occur more than 20 years before symptom onset and somewhat earlier than was suggested by findings from previous MRI studies," Nick Fox of the University College London's Dementia Research Centre said in a comment on the study.

Alzheimer's disease causes two-thirds of dementia cases -- attacking one in 200 people -- the rate is increasing as the world's population ages.

Trial participants, 20 with the fateful gene mutation and 24 without, were not told whether they had it or not. All had normal cognitive abilities at the time of the study.

"The findings... could ultimately lead to improved early detection and better clinical trials of preventative treatments," The Lancet said in a statement.

But the outcome also raises questions about scientists' understanding of how Alzheimer's progresses.

"These findings... raise new questions about the earliest brain changes involved in the predisposition to Alzheimer's and the extent to which they could be targeted by future prevention therapies," research leader Eric Reiman from the Banner Alzheimer's Institute in Arizona said.

Scientists still do not know quite what to make of the plaques and tangles that German doctor Alois Alzheimer first spotted in the brain of a dementia patient who died in 1906.

They disagree on the respective roles of beta amyloid plaque build-ups and of a protein called tau which forms tangles inside the brain cells.

Most test therapies have targeted beta amyloids, but some now suggest it is actually tau killing the brain cells.

According to Fox, the new study questioned existing models of Alzheimer's Disease "on several fronts".

Among other things, "neurodegeneration would seem to be occurring in advance of evidence of plaque deposition", widely thought to cause the brain damage.

Fox said the results should be treated with caution as the trial sample was small and the outcome may not apply to the much more common sporadic, late-onset form of Alzheimer's.

Alzheimer's Disease International (ADI) projects the number of people with dementia will rise from 35.6 million in 2010 to 65.7 million by 2030 and 115.4 million by 2050.


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Alzheimer's may be detectable earlier than thought

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Tuesday, February 28, 2012

Alzheimer's: French scientists focus on key target

Day by day, science is finding help for the aged; what will it be when come my time?

Posted: 25 January 2012

An aged person (AFP/File/Sebastien Bozon)
PARIS: French scientists said on Tuesday that lack of a key brain protein was linked to Alzheimer's, a finding that threw up a tempting target for drugs to fight the disease.

"What we've found is a weapon for controlling and modifying tau," said Etienne-Emile Baulieu of France's National Institute of Health and Medical Research (Inserm), referring to a culprit involved in Alzheimer's.

Building on earlier work, researchers delved into a Paris "brain bank," of organs donated for medical science, to compare levels of a protein called FKBP52 among brains of people who had died of dementia and those who had died of other causes.

Tiny slivers of brain were extracted and their chemicals analysed.

In the frontal cortex, "levels of FKBP52 were 75 percent lower among people who had died of Alzheimer's and other tau diseases, a dramatic fall," Baulieu told a press conference.

Baulieu said FKBP52 was the best target that had surfaced so far in the fight against Alzheimer's, a disease that is as cruel as it is baffling.

A rogue protein that later became named tau was first spotted in 1912 by Alois Alzheimer, the German neuropathologist who gave his name to this relentless degenerative disease of the brain.

When normal tau undergoes a process called hyperphosphorylation, it starts to assemble in microscopic tangles inside brain cells, killing them.

But another telltale sign of Alzheimer's is the accumulation of so-called amyloid plaques outside neurons, and their connection with tau, if any, remains unclear.

Discovered in 1992, FKBP52 is a protein that is found abundantly in the brain, where it has a workhorse role in folding and unfolding other proteins.

But it has also been revealed to bind to tau, which gives rise to the theory that lack of the protein helps tau to clump together.

Baulieu sounded a word of caution, saying the molecular cascade of events that cause tau tangles was still not fully clear.

But levels of FKBP52 could be used as a marker of susceptibility to Alzheimer's, and boosting them could provide a means of stalling progression of the disease.

"I think that in three or four years, we will have results that are sufficiently broad and robust to be able to use candidate drugs that we will have found, or that pharmaceutical companies can use and modify," he said.

"It may go a lot faster than people say."

In 2010, Alzheimer's Disease International, the umbrella body of national associations for the disease, estimated that the number of Alzheimer's sufferers will mushroom from 35.6 million people worldwide to 65.7 million by 2030 and 115.4 million by 2050.

The research appears in the Journal of Alzheimer's Disease.

- AFP/al

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Alzheimer's: French scientists focus on key target

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