Gene Variation May Protect Against Alzheimer’s: Study

A breakthrough study has identified a class of natural gene variants that may protect against Alzheimer’s disease.

For the study, researchers at University College London analyzed DNA from more than 10,000 people — half with Alzheimer’s and half without. The investigators found that these gene variants reduce the functioning of proteins called tyrosine phosphatases.

These proteins impair the activity of a cell signaling pathway important for cell survival, explained the authors of the study published online Feb. 5 in the Annals of Human Genetics.

The pathway could be a key target for drugs to treat Alzheimer’s, and the study authors said that the findings provide more evidence that other genes may be linked to one’s risk for the memory disorder.

“These results are quite encouraging. It looks as though when naturally occurring genetic variants reduce the activity of tyrosine phosphatases, then this makes Alzheimer’s disease less likely to develop, suggesting that drugs which have the same effect might also be protective,” lead author David Curtis said in a college news release. He’s a professor of genetics, evolution and environment.

Previous research in mice and rats suggested that inhibiting the function of these proteins might help protect against Alzheimer’s, but this study is the first to find such an effect in people.

There are already drugs that target tyrosine phosphatases, but they haven’t been tested in human clinical trials, Curtis noted.

“Here’s a natural experiment in people that helps us understand how Alzheimer’s disease develops: as some people have these genetic variants and some don’t, we can see that the impact of having particular variants is a reduced likelihood of developing Alzheimer’s disease,” he said.

Evidence also suggests that genetic variants that damage the gene for the PI3K protein are associated with an increased risk of Alzheimer’s.

“There is a consistent story in our results that the activity of the … signaling pathway is protective, which is exactly in line with findings from animal studies,” Curtis said.

Source: HealthDay

Living Near Major Roads Linked to Increased Risk of Dementia, Parkinson’s, Alzheimer’s and MS

Living near major roads or highways is linked to higher incidence of dementia, Parkinson’s disease, Alzheimer’s disease and multiple sclerosis (MS), suggests new research published this week in the journal Environmental Health.

Researchers from the University of British Columbia analyzed data for 678,000 adults in Metro Vancouver. They found that living less than 50 metres from a major road or less than 150 metres from a highway is associated with a higher risk of developing dementia, Parkinson’s, Alzheimer’s and MS—likely due to increased exposure to air pollution.

The researchers also found that living near green spaces, like parks, has protective effects against developing these neurological disorders.

“For the first time, we have confirmed a link between air pollution and traffic proximity with a higher risk of dementia, Parkinson’s, Alzheimer’s and MS at the population level,” says Weiran Yuchi, the study’s lead author and a PhD candidate in the UBC school of population and public health. “The good news is that green spaces appear to have some protective effects in reducing the risk of developing one or more of these disorders. More research is needed, but our findings do suggest that urban planning efforts to increase accessibility to green spaces and to reduce motor vehicle traffic would be beneficial for neurological health.”

Neurological disorders—a term that describes a range of disorders, including Alzheimer’s disease and other dementias, Parkinson’s disease, multiple sclerosis and motor neuron diseases—are increasingly recognized as one of the leading causes of death and disability worldwide. Little is known about the risk factors associated with neurological disorders, the majority of which are incurable and typically worsen over time.

For the study, researchers analyzed data for 678,000 adults between the ages of 45 and 84 who lived in Metro Vancouver from 1994 to 1998 and during a follow-up period from 1999 to 2003. They estimated individual exposures to road proximity, air pollution, noise and greenness at each person’s residence using postal code data. During the follow-up period, the researchers identified 13,170 cases of non-Alzheimer’s dementia, 4,201 cases of Parkinson’s disease, 1,277 cases of Alzheimer’s disease and 658 cases of MS.

For non-Alzheimer’s dementia and Parkinson’s disease specifically, living near major roads or a highway was associated with 14 per cent and seven per cent increased risk of both conditions, respectively. Due to relatively low numbers of Alzheimer’s and MS cases in Metro Vancouver compared to non-Alzheimer’s dementia and Parkinson’s disease, the researchers did not identify associations between air pollution and increased risk of these two disorders. However, they are now analyzing Canada-wide data and are hopeful the larger dataset will provide more information on the effects of air pollution on Alzheimer’s disease and MS.

When the researchers accounted for green space, they found the effect of air pollution on the neurological disorders was mitigated. The researchers suggest that this protective effect could be due to several factors.

“For people who are exposed to a higher level of green space, they are more likely to be physically active and may also have more social interactions,” said Michael Brauer, the study’s senior author and professor in the UBC school of population and public health. “There may even be benefits from just the visual aspects of vegetation.”

Brauer added that the findings underscore the importance for city planners to ensure they incorporate greenery and parks when planning and developing residential neighbourhoods.

Source: University of British Columbia


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More Doubt That Plaques in the Brain Cause Alzheimer’s

For decades, scientists have known that Alzheimer’s disease is accompanied by the buildup of clumps of amyloid protein between brain cells. Could these plaques be causing the disease?

That’s been a prevailing theory driving Alzheimer’s research for years. But a new study suggests the strategy could be wrong.

Researchers reporting in the journal Neurology have found that early declines in memory and thinking seen in Alzheimer’s patients tend to occur before amyloid plaques begin to appear in the brain, not after.

“Our research was able to detect subtle thinking and memory differences in study participants and these participants had faster amyloid accumulation on brain scans over time, suggesting that amyloid may not necessarily come first in the Alzheimer’s disease process,” study author Kelsey Thomas explained in a journal news release.

“Much of the research exploring possible treatments for Alzheimer’s disease has focused on targeting amyloid, but based on our findings, perhaps that focus needs to shift to other possible targets,” said Thomas, who conducts research at the VA San Diego Healthcare System.

This isn’t the first indication that amyloid plaques might not cause Alzheimer’s disease.

In April, clinical trial data on an experimental Alzheimer’s drug called verubecestat was published in the New England Journal of Medicine. The drug reduced amyloid plaque levels in patients’ brains and spinal fluid.

However, despite those reductions, patients showed no easing or slowing of their disease.

Those negative results present “pretty strong evidence that amyloid-lowering is the wrong target,” Dr. David Knopman, a professor of neurology with the Mayo Clinic in Rochester, Minn., said at the time. “They hit the target and yet people got worse, consistently worse, both in terms of brain structure and brain cognition,” he added.

Similar poor results were seen with another amyloid-focused drug, aducanumab. Studies on the drug were halted earlier this year because it didn’t appear to be effective. However, in December it was announced that research into aducanumab might resume.

In the new study, Thomas and her team tracked the neurological health of 747 people, average age 72 years. Everyone got a barrage of tests to spot and follow any changes — even subtle ones — in their memory and thinking skills.

Based on test results, 305 people were deemed to have normal thinking and memory skills, 153 had very subtle thinking and memory differences, and 289 people had mild cognitive impairment — often a precursor to Alzheimer’s disease.

The participants also underwent high-tech brain scans at the beginning of the study and then yearly scans over the next four years, looking for signs of amyloid plaque buildup.

The investigators found that amyloid plaque accumulation occurred no faster in people with mild cognitive impairment than it did in people with normal thinking and memory skills.

Other brain changes were seen in conjunction with mild cognitive impairment, however, such as faster thinning of the brain’s entorhinal cortex, as well as brain shrinkage of the hippocampus. Both brain regions are key to memory.

And there could be another culprit at work in Alzheimer’s development, Thomas said.

“From prior research, we know that another biomarker of Alzheimer’s disease, a [brain] protein called tau, shows a consistent relationship with thinking and memory symptoms,” she said. “Therefore, more research is needed to determine if tau is already present in the brain when subtle thinking and memory differences begin to appear.”

The study might lead to a better way to calculate a person’s risk for Alzheimer’s, Thomas added.

“Our study demonstrated a method to successfully detect subtle differences in thinking and memory either before or during the phase when amyloid is accumulating at a faster rate,” she explained. “This could lead to noninvasive screenings that may be able to detect very early who is at risk of developing Alzheimer’s disease.”

One neurologist unconnected to the new study agreed that it helps point to new and potentially fruitful avenues of research.

The thinking that amyloid plaque buildup “leads to clinical problems is no longer a valid one, as this study demonstrates,” said Dr. Gayatri Devi, a neurologist and psychiatrist at Lenox Hill Hospital in New York City.

“Subtle symptoms accompanying or even preceding brain pathology suggest that numerous other factors are involved in the complex risk mixture that leads to Alzheimer’s disease,” Devi said.

Source: HealthDay

Obesity in Middle Age Could Raise Odds for Alzheimer’s Later

Dennis Thompson wrote . . . . . . . . .

Obesity in middle age is associated with an increased risk of dementia later in life, according to a study of more than 1 million women in the United Kingdom.

Those who were obese in their mid-50s had 21% greater risk of being diagnosed with dementia 15 or more years later, compared with women who had a healthy weight, a team of British and international researchers found.

The study adds to the “ever-expanding body of data that says what you do with yourself in midlife — and really even earlier — affects your risk for dementia as you age,” said Keith Fargo, director of scientific programs and outreach at the Alzheimer’s Association in Chicago. He was not part of the research.

For the study, the researchers followed about 1 out of every 4 women born in the United Kingdom between 1935 and 1950, more than 1.1 million overall. Their average age at the start of the study was 56. None had dementia.

At the outset, researchers calculated each woman’s body mass index (BMI), an estimate of body fat based on height and weight. They also asked about their diet and exercise. The women were followed for an average 18 years.

During that time, about 2.1% of obese women were diagnosed with dementia, compared to 1.6% of normal-weight women, the researchers found.

The study was published online in the journal Neurology.

A lot of factors associated with obesity are bad for the brain, said Dr. Gayatri Devi, a neurologist and psychiatrist who specializes in memory disorders at Northwell Health in New York City.

These include high cholesterol, elevated levels of inflammation and increased stroke risk, said Devi, who was not involved with the study. Obese people tend to suffer poor sleep due to sleep apnea, and their brains struggle to get enough oxygen to function properly.

Fargo agreed.

“You’re essentially beating your brain up when you’re obese, because your brain requires a lot of oxygen and a lot of nutrients to function day-to-day and maintain structural integrity,” he said. “Anything that challenges the body’s ability to maintain the proper function and structure of the brain is going to increase your risk for developing cognitive decline as you age.”

The researchers also looked to see if physical inactivity or an inadequate low-calorie diet were linked to dementia. They found no significant associations.

Low calorie intake and inactivity were associated with higher dementia risk during the first 10 years of the study, but the link weakened in subsequent years until it became insignificant, the study found.

“Other studies have shown that people become inactive and lose weight up to a decade before they are diagnosed with dementia,” lead researcher Sarah Floud, of the University of Oxford, said in a journal news release. “The short-term links between dementia, inactivity and low calorie intake are likely to be the result of the earliest signs of the disease, before symptoms start to show.”

But Fargo said he doesn’t put much stock into those findings, given that the study was relatively short and the fact that diet and exercise are so closely linked with obesity.

“If you have obesity at 56, chances are your diet and physical activity pattern hasn’t been all that great for potentially decades at that point,” he said. “I think it’s a little difficult to disentangle the obesity story and the physical activity/diet story, especially given that they only measured physical activity and diet one time, right at the intake into the study. No one really knows what was happening with these individuals’ diet and physical activity levels in that intervening 15 to 20 years.”

It’s also impossible to tell from this study whether losing weight, eating right and exercising in middle age will reduce your later dementia risk, Fargo said. Ongoing clinical trials are expected to shed light on that question.

Devi, however, said she is “absolutely” convinced that an obese person who loses weight in midlife improves his or her chances of avoiding dementia.

“I think there is never not a good time to improve general physical and cardiovascular health, improve brain health and reduce risk for Alzheimer’s,” Devi said.

Source: HealthDay


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China Gives Conditional OK to Its First Self-developed Alzheimer’s Drug

China has granted conditional approval to its first self-developed treatment for Alzheimer’s disease, a move that may point to revived opportunities in a therapeutic area where drugmakers have burned billions of dollars without yielding a validated new drug.

Oligomannate, which uses extract from marine brown algae as raw material, received a conditional green light to treat mild-to-moderate level AD, the National Medical Products Administration (NMPA) said in a statement on its website late on Saturday.

An effective treatment for Alzheimer’s, which is estimated in 60%-70% of around 50 million dementia cases worldwide, could become one of the best-selling drugs globally.

“Trial results demonstrated that Oligomannate statistically improved cognitive function in mild-to-moderate AD patients as early as week 4 and the benefit was sustained at each follow-up assessment visit,” Shanghai Green Valley Pharmaceuticals, which developed the drug along with two academic institutions in China, said in a statement.

The outlook for a cure is clouded with theoretical uncertainties and high-profile failures. Pharmaceutical giants including Johnson & Johnson, Merck and Pfizer have ditched their projects on unsatisfactory data.

Biogen last month revived its plans to seek U.S. approval for its aducanumab treatment after announcing in March that it would terminate two large clinical trials for the drug. But some analysts believed FDA approval is highly unlikely.

China is fast-tracking approval for innovative drugs at home in a bid to offer more and cheaper options to patients, as many in the rapidly aging country struggle to find alternatives to costly treatments sold by multinational pharmaceutical firms for chronic diseases.

In an August overhaul to its drug administration law, Beijing said conditional approval could be granted to some still-under-research medicines of “predictable” clinical value for life-threatening diseases for which effective treatment is not immediately available.

Further research on Oligomannate’s pharmacological mechanism and long-term safety and effectiveness is required, according to the NMPA statement.

Green Valley said it would launch the drug “very soon” in China. The company also aims to roll out a phase-3 clinical trial with sites in the United States, Europe and Asia in early 2020 to facilitate global regulatory approval of the drug.

Source : Reuters


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