Researchers Suggest New Theory for How Parkinson’s Disease Develops

Newswise, May 20, 2017— The toxic protein behind Parkinson’s disease may not spread like an infection from nerve cell to nerve, according to a new theory by Technion and Harvard University scientists. Instead, the protein, called alpha-synuclein, may simultaneously affect all parts of the nervous system inside and outside of the brain. Their findings could change how Parkinson’s is treated, the researchers say.

Associate Professor Simone Engelender of the Technion-Israel Institute of Technology and her colleague Ole Isacson at Harvard Medical School describe this “threshold theory” of Parkinson’s for the first time in a report published in the January issue of Trends in Neuroscience.

“Instead of studying how proteins move from one neuron to another and searching for compounds that prevent the ‘spread’ of aggregated α-synuclein, we need to study why α-synuclein accumulates within neurons and how these neurons die in the disease, and search for compounds that prevent the general neuronal dysfunction,” said Professor Engelender.

Parkinson’s disease destroys nerve cells throughout the body, especially key neurons in the brain that produce a compound called dopamine that helps to control movement and posture.

The disease grows worse over time, and there is no known cure. More than one million people in the United States have the disorder, according to the Parkinson’s Disease Foundation.

The disease is caused by accumulation of α-synuclein, which overwhelms and destroys nerve cells. The most commonly-held theory about the disease suggests that patients get progressively worse as clumps of α-synuclein spread between neurons, almost like an infection.

But Engelender and Isacson think the scientific evidence points to a different model of the disease. Instead of spreading from neuron to neuron, they say, aggregations of α-synuclein develop throughout the body at the same time.

Different parts of the nervous system vary in how much of this toxic protein they can tolerate, depending on how well the cells in that part of the system work together to compensate for any destroyed cells.

The researchers say their theory fits better with patients’ symptoms than the infection-style theory. Engelender and Isacson’s theory may help explain, for example, why some of the earliest signs of the disease appear in places like the gastrointestinal tract that have no neurons to compensate for a dysfunction and therefore have a lower threshold of tolerance for α-synuclein toxicity.

The new theory may also affect how the disease is treated. For instance, some scientists have recommended a procedure that severs part of the vagus nerve, which runs outside the brain, to prevent the spread of α-synuclein from the body to the brain. The threshold theory, Engelender said, suggests that this operation would be unnecessary.

“The only specific treatment that is and will continue to be beneficial is the replenishment of dopamine in the brain, through the intake of the supplement L-Dopa, to improve the motor symptoms,” said Engelender.

“This has been done for several decades and should be continued to be done since it can at least alleviate the motor symptoms for a few years, even if does not cure and does not prevent the progression of the disease.”

“Nevertheless, I believe that the search for compounds that specifically decrease α-synuclein levels are the only hope to provide a real and more effective treatment for the disease,” Engelender added.

The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s renown as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Institute is a vital component of Cornell Tech, and a model for graduate applied science education that is expected to transform New York City’s economy. American Technion Society (ATS) donors provide critical support for the Technion—more than $2 billion since its inception in 1940. Based in New York City, the ATS and its network of supporters across the U.S. provide funds for scholarships, fellowships, faculty recruitment and chairs, research, buildings, laboratories, classrooms and dormitories, and more.

Women May Keep Verbal Memory Skills Longer than Men in the Early Stages of Alzheimer’s

Newswise, March 18, 2016 – Women may have a better memory for words than men despite evidence of similar levels of shrinkage in areas of the brain that show the earliest signs of Alzheimer’s disease, according to a study published in the March 16, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology

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According to study author Erin E. Sundermann, PhD, of Albert Einstein College of Medicine in Bronx, NY, “One way to interpret the results is that because women have better verbal memory skills than men throughout life, women have a buffer of protection against loss of verbal memory before the effects of Alzheimer’s disease kick in.

Because verbal memory tests are used to diagnose people with Alzheimer’s disease and its precursor, mild cognitive impairment, these tests may fail to detect mild cognitive impairment and Alzheimer’s disease in women until they are further along in the disease.”

The study included participants from the Alzheimer’s Disease Neuroimaging Initiative: 235 people with Alzheimer’s disease, 694 people with mild cognitive impairment that included memory problems, and 379 people with no memory or thinking problems. The groups’ performance on a test of verbal memory was compared to the size of the hippocampal area of the brain, which is responsible for verbal memory and affected in the early stages of Alzheimer’s disease.

Women performed better than men on the tests of both immediate recall and delayed recall among those showing evidence of minimal to moderate amounts of hippocampal shrinkage.

At the high level of hippocampal shrinkage, there was no difference in the scores of men and women. At the score that indicates the start of verbal memory impairment, or 37 on a scale of zero to 75 for immediate recall, women showed greater evidence of hippocampal shrinkage (ratio of hippocampal volume to total brain volume multiplied by 103 was 5 compared to 6 for men).

Mary Sano, PhD, of Icahn School of Medicine at Mount Sinai in New York, NY, and a member of the American Academy of Neurology, said in a corresponding editorial, “At a public policy level, the potential health care cost for under-detection or delayed diagnosis of women with Alzheimer’s disease or its early stages is staggering and should motivate funding in this area.”

“If these results are confirmed, then we may need to adjust memory tests to account for the difference between men and women in order to improve our accuracy in diagnosis,” said Sundermann.

The Alzheimer’s Disease Neuroimaging Initiative was supported by the National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, U.S. Food and Drug Administration, Abbott, Amorfix Life Sciences, AstraZeneca, Bayer HealthCare, BioClinica, Biogen Idec, Bristol-Myers Squibb, Eisai, Elan Pharmaceuticals, Eli Lilly, F. Hoffmann-La Roche and Genentech, GE Healthcare, Innogenetics, IXICO, Janssen Alzheimer Immunotherapy Research and Development, Johnson and Johnson Pharmaceutical Research and Development, Medpace, Merck, Meso Scale Diagnostics, Novartis Pharmaceuticals; Pfizer, Servier, Synarc and Takeda Pharmaceutical.

To learn more about Alzheimer’s disease, please visit www.aan.com/patients.

The American Academy of Neurology, an association of 30,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson’s disease and epilepsy.

Alzheimer’s Plaques Found in Middle-Aged People with Brain Injuries

Newswise, March 18, 2016 —  A new study suggests that people with brain injuries following head trauma may have buildup of the plaques related to Alzheimer’s disease in their brains. The research is published in the  online issue of Neurology®, the medical journal of the American Academy of Neurology.

A corresponding editorial states that over the past decade the rate of emergency department visits related to traumatic brain injury (TBI) has increased by 70 percent. The editorial also says an estimated three to five million Americans live with a TBI-related disability.

“The study is small and the findings preliminary, however, we did find an increased buildup of amyloid plaques in people who had previously sustained a traumatic brain injury,” said study author Professor David Sharp, MD, of Imperial College London, in the United Kingdom.

 “The areas of the brain affected by plaques overlapped those areas affected in Alzheimer’s disease, but other areas were involved. People after a head injury are more likely to develop dementia, but it isn’t clear why. Our findings suggest TBI leads to the development of the plaques which are a well-known feature of Alzheimer’s disease.”

For the study, nine people with an average age of 44 who had a single moderate to severe TBI had PET and MRI brain scans. The brain injuries occurred between 11 months and up to 17 years before the start of the study. The participants were compared to 10 people with Alzheimer’s disease and nine healthy participants.

The PET scans used a marker that detects plaques in the brain. The MRI scans used diffusion tensor imaging to detect damage to brain cells that occurs after TBI. Both the people with brain injuries and the people with Alzheimer’s disease had plaques in the posterior cingulate cortex, which is affected early in Alzheimer’s, but only those with brain injuries had plaques in the cerebellum. The researchers also found that plaques were increased in patients with more damage to the brain’s white matter.

“It suggests that plaques are triggered by a different mechanism after a traumatic brain injury,” Sharp said. “The damage to the brain’s white matter at the time of the injury may act as a trigger for plaque production.”

“If a link between brain injury and later Alzheimer’s disease is confirmed in larger studies, neurologists may be able to find prevention and treatment strategies to stave off the disease earlier,” said Sharp.

The study was supported by the Imperial College Healthcare Trust Biomedical Research
Center.

To learn more about Alzheimer’s disease, please visit www.aan.com/patients.

The American Academy of Neurology, an association of 30,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson’s disease and epilepsy.

Couch Potatoes May Have Smaller Brains Later in Life

Newswise, February 13, 2016– Poor physical fitness in middle age may be linked to a smaller brain size 20 years later, according to a study published in the February 10, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“We found a direct correlation in our study between poor fitness and brain volume decades later, which indicates accelerated brain aging,” said study author Nicole Spartano, PhD, with Boston University School of Medicine in Boston.

For the study, 1,583 people enrolled in the Framingham Heart Study, with an average age of 40 and without dementia or heart disease, took a treadmill test.

They took another one two decades later, along with MRI brain scans. The researchers also analyzed the results when they excluded participants who developed heart disease or started taking beta blockers to control blood pressure or heart problems; this group had 1,094 people.

The participants had an average estimated exercise capacity of 39 mL/kg/min, which is also known as peak VO2, or the maximum amount of oxygen the body is capable of using in one minute.

Exercise capacity was estimated using the length of time participants were able to exercise on the treadmill before their heart rate reached a certain level.

For every eight units lower a person performed on the treadmill test, their brain volume two decades later was smaller, equivalent to two years of accelerated brain aging.

When the people with heart disease or those taking beta blockers were excluded, every eight units of lower physical performance was associated with reductions of brain volume equal to one year of accelerated brain aging.

The study also showed that people whose blood pressure and heart rate went up at a higher rate during exercise also were more likely to have smaller brain volumes two decades later.

Spartano said that people with poor physical fitness often have higher blood pressure and heart rate responses to low levels of exercise compared to people with better fitness.

Spartano noted that the study is observational. It does not prove that poor physical fitness causes a loss of brain volume; it shows the association.

“While not yet studied on a large scale, these results suggest that fitness in middle age may be particularly important for the many millions of people around the world who already have evidence of heart disease,” she said.

The study was supported by the National Heart, Lung and Blood Institute, the National Institutes of Health and the American Heart Association.

To learn more about brain health, please visit www.aan.com/patients.

The American Academy of Neurology, an association of 30,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson’s disease and epilepsy.