Is this the Alzheimer's gene?
Scientists find gene that raises risk of condition 12-fold
By Danielle Zoellner For Dailymail.com
PUBLISHED: 18:00 BST, 20 September 2017 | UPDATED: 18:00 BST, 20 September 2017
Researchers from Washington University School of Medicine in St. Louis studied the gene ApoE4 and its impact on the brain
The mutant gene was discovered in 1993 and has been a mystery since for how it causes an increase in Alzheimer's for people
It is linked to brain damage from knots of protein in the neurons of the brain Experts say targeting this gene could help suppress the neurological disease
Scientists have identified the gene that increases the risk of Alzheimer's disease up to 12 times and how they can suppress it, a study claims.
ApoE4 is a genetic variant known to increase a person's chances for developing the neurodegenerative disease.
The mutant gene is directly linked to brain damage caused by knots of protein within neurons called tau tangles. The tangles were found to less harmful without ApoE4.
They believe targeting the gene could theoretically prevent the neurological destruction caused by Alzheimer's, for which there is currently no cure.
An estimated five-and-a-half million people in the United States suffer from Alzheimer's, according to the Alzheimer's Association.
Experts say this discovery could pave the way for treatments that will slow down or halt the disease that causes loss of memory and cognitive function.
Researchers from Washington University School of Medicine in St. Louis, Missouri, studied ApoE4 after it was first discovered in 1993.
The gene has been known as a 'time bomb' for the disease but has remained a mystery on how it impairs the brain until now.
The presence of the gene increases the brain damage caused by toxic tangles of a different Alzheimer's-associated protein: tau. In its absence, tau tangles did very little harm to brain cells.
'Once tau accumulates, the brain degenerates,' said senior author Dr David Holtzman, head of the Department of Neurology at Washington University.
What we found was that when ApoE is there, it amplifies the toxic function of tau, which means that if we can reduce ApoE levels we may be able to stop the disease process.'
Alzheimer's, which affects one in 10 people over age 65, is the most common example of a family of diseases called tauopathies.
To find out what effect ApoE variants have on tauopathies, Holtzman and his team turned to genetically modified mice that carry a mutant form of human tau prone to forming toxic tangles.
They compared mice that lacked any version of the gene or were engineered to have one of three human variants, ApoE2, ApoE3 or ApoE4.
By the time they were nine months old, mice carrying the human variants had suffered widespread brain damage.
The hippocampus and entorhinal cortex, which are responsible for memory, were shrunken, and the fluid-filled space of the brain had enlarged where the dead cells had been.
ApoE4 mice exhibited the most severe neurodegeneration, and ApoE2 the least. The mice that lacked the gene entirely showed virtually no brain damage.
'ApoE4 seems to be causing more damage than the other variants because it is instigating a much higher inflammatory response, and it is likely the inflammation that is causing injury,' Holtzman said.
'But all forms of ApoE - even ApoE2 - are harmful to some extent when tau is aggregating and accumulating. The best thing seems to be in this setting to have no ApoE at all in the brain.'
A follow-up study of brain tissue samples from 79 people who had died from tau-related conditions other than Alzheimer's showed greater levels of damage in those who had ApoE4.
The gene transports cholesterol around the body via the bloodstream.
A few, rare individuals lack a functional ApoE gene. Such people have very high cholesterol levels and, if untreated, die young of cardiovascular disease. The lack of the gene in their brains, however, creates no obvious problems.
'There are people walking around who have no ApoE and they're fine cognitively,' Holtzman said. 'It doesn't appear to be required for normal brain function.'
These findings suggest that decreasing ApoE specifically in the brain could slow or block neurodegeneration, even in people who already have accumulated tau tangles.
'Assuming that our findings are replicated by others, I think that reducing ApoE in the brain in people who are in the earliest stages of disease could prevent further neurodegeneration,' Holtzman said.
http://www.dailymail.co.uk/health/article-4903370/Alzheimer-s-gene-scientists-decrease-symptoms.html#ixzz4tJSSIENH
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Iron levels in brain predict when people will get Alzheimer's
16:56 19 May 2015 by Clare Wilson
Does this qualify as irony? Our bodies need iron to be healthy – but too much could harm our brains by bringing on Alzheimer's disease.
If that's the case, measuring people's brain iron levels could help identify those at risk of developing the disease. And since we already have drugs that lower iron, we may be able to put the brakes on.
Despite intense efforts, the mechanisms behind this form of dementia are still poorly understood. For a long time the main suspect has been a protein called beta-amyloid, which forms distinctive plaques in the brain, but drugs that dissolve it don't
result in people improving.
Not so good ferrous
Studies have suggested that people with Alzheimer's also have higher iron levels in their brains. Now it seems that high iron may hasten the disease's onset.
Researchers at the University of Melbourne in Australia followed 144 older people who had mild cognitive impairment for seven years. To gauge how much iron was in their brains, they measured ferritin, a protein that binds to the metal, in their
cerebrospinal fluid. For every nanogram per millilitre people had at the start of the study, they were diagnosed with Alzheimer's on average three months earlier.
The team also found that the biggest risk gene for Alzheimer's, ApoE4, was strongly linked with higher iron, suggesting this is why carrying the gene makes you more vulnerable.
Iron is highly reactive, so it probably subjects neurons to chemical stress, says team member Scott Ayton.
Anti-iron drugs
The finding by itself doesn't prove that reducing iron levels would cut people's risk of Alzheimer's but a trial of a drug that rids the body of some of its iron, carried out 24 years ago, suggests it's a hypothesis worth investigating.
The drug halved the rate of Alzheimer's cognitive decline but was overlooked when the beta-amyloid theory of the disease became dominant, says Ayton. "Perhaps it's time to refocus the field on looking at iron as a target," he says.
One easy way of reducing iron levels - having regular blood donations - would not be a good idea for older people as it can bring on anaemia. Also, says Ayton, "there is only a modest correlation between iron levels in the blood and in the brain."
However, there is an iron-binding drug called deferiprone which gets into the brain and reduces levels of the metal there without disturbing blood levels too much. It is used to treat cases of iron poisoning and has also been found to slow the
progression of Parkinson's disease, another condition in which high iron levels have been implicated.
Journal reference: Nature Communications, DOI: 10.1038/ncomms7760
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