Blocking protein that impairs brain’s clean-up crew improves old mice’s smarts

We need this. Or is young blood a better way to improve cognition?

Young Blood Revitalizes the Aging Brain June 2014 

I bet this from Feb. 2016 was never followed up on.

 Improving Brain’s Garbage Disposal May Slow Alzheimer’s Disease

Or this from Sept. 2013?

When brain’s trash collectors fall down on the job, neurodegeneration risk picks up

 

 

Blocking protein that impairs brain’s clean-up crew improves old mice’s smarts

Author Bruce GoldmanPublished on April 3, 2019

Stanford neuroscientist Tony Wyss-Coray, PhD, has been working for several years on the question of what causes the brain to lose its acuity with advancing age. One focus of his research has been a class of brain cells called microglia, which serve as the brain's immune cells.
A less-vaunted microglial function is more akin to that of a garbage crew. Among the many different things microglia do to keep the brain healthy is scarfing up bits of cellular debris and protein deposits that build up like so much dandruff in the course of normal metabolic activity.
Bits of myelin debris -- remnants of decaying nerve-cell coatings that, by providing electrical insulation, speed the transmission of impulses along nerve tracts -- commonly accumulate in aging brains. Aging-associated aggregation of a protein fragment called beta-amyloid into gummy deposits in the brain are considered a hallmark of Alzheimer's disease. Likewise with clumps of yet another substance, alpha-synuclein, associated with Parkinson's disease.
These accumulations occur over time largely because, as I wrote in my news release about a study published in Nature by Wyss-Coray and his colleagues:

[T]he garbage-collecting performance of microglia diminishes in aging brains. Why this happens, and the extent to which the faulty garbage service is actually responsible for age-related cognitive losses, are unclear. But it's a decent bet that one way or another, microglial malperformance plays a role in neurodegeneration.

In a series of sophisticated experiments, Wyss-Coray's team identified a single protein called CD22 that, in the brain, is found only on the surfaces of microglial cells; becomes increasingly abundant with increasing age (in mice, at least); and, when activated, profoundly impairs these cells from performing their debris-cleanup role.
Then, the researchers conducted another set of experiments. Into one side of mice's brains, they injected specialized proteins (called antibodies) capable of blocking CD22's activity without otherwise disrupting brain function. Into the mirror-image spot on the other side of the mice's brains, they injected otherwise identical antibodies that, however, lacked the ability to block CD22.
Along with the antibodies, the scientists injected bits of myelin -- like sprinkling some confetti around to test a new vacuum cleaner. On inspection two days later, the myelin debris was much less prevalent on the side of mice's brains where "working" antibodies rather than "dummy" antibodies to CD22 had been injected.
The same thing happened when instead of myelin debris, the researchers injected beta-amyloid or alpha-synuclein, the Alzheimer's- and Parkinson's-associated substances.
In all three cases, microglia exposed to CD22-blocking antibodies outperformed their fellow microglia on the opposite side of the brain in ingesting the neurodegeneration-linked substances.
Then, the researchers lengthened the period of exposure from 48 hours to a full month. From my news release:

They reconfigured their injection technique to provide continuous CD22-blocking antibody infusion on both sides of the brain over this period. ... [O]ld mice receiving these infusions outperformed control mice of the same age on two different tests of learning and memory that are commonly used to assess mice's cognitive ability.

"The mice became smarter," Wyss-Coray told me. "Blocking CD22 on their microglia restored their cognitive function to the level of younger mice."
He thinks CD22 could prove to be a brand-new target for treatment of neurodegenerative diseases.

Improving Brain’s Garbage Disposal May Slow Alzheimer’s Disease

We need this and soon. But because we have NO stroke leadership or strategy nothing will get done on this.
Your 33% dementia chance post-stroke from an Australian study?  May 2012.
Then this study came out and seems to have a range from 17-66%. December 2013.
A 20% chance in this research.   July 2013.
http://medicalxpress.com/news/2015-01-scientists-heart-disease-clues-alzheimer.html

 Improving Brain’s Garbage Disposal May Slow Alzheimer’s Disease

A drug that boosts activity in the brain’s “garbage disposal” system can decrease levels of toxic proteins associated with Alzheimer’s disease and other neurodegenerative disorders and improve cognition in mice, a new study by neuroscientists at Columbia University Medical Center (CUMC) and New York State Psychiatric Institute (NYSPI) has found. The study was published today in the online edition of Nature Medicine.

“We have identified a new way to activate the brain’s garbage disposal system, and have shown that we can effectively use a drug to activate this system and slow down disease in a mouse model,” said study leader Karen E. Duff, PhD, professor of pathology and cell biology (in psychiatry and in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at CUMC and NYSPI. “This has the potential to open up new avenues of treatment for Alzheimer’s and many other neurodegenerative diseases.”
The drug used was rolipram, which causes nausea and thus is not a good drug for use in humans. However, similar drugs do not incur nausea as a side effect and can be potentially tested in clinical trials quickly.
To remain healthy, brain cells must continually clear out old, worn, or damaged proteins, a task performed by a small molecular cylinder called the proteasome. The proteasome acts as a kind of garbage disposal, grinding up the old proteins so they can be recycled into new ones. In neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, proteins tagged for destruction accumulate in the brain’s neurons, suggesting that the cell’s proteasomes are impaired.
Using a genetically engineered mouse, the researchers first discovered that tau—a protein that accumulates in Alzheimer’s, frontotemporal degeneration, and other brain diseases—sticks to the proteasome and slows down the protein disposal process.
“Something profoundly bad happens to proteasomes in diseases where abnormal proteins accumulate,” said the study’s first author, Natura Myeku, PhD, an associate research scientist in the pathology and cell biology department at CUMC. “Our work on tau showed that even when proteasomes are removed from the diseased brains they remain defective and can’t chew up proteins compared with proteasome from normal brains.”
Administering rolipram activated the proteasome and restored protein disposal. The drug also improved memory in diseased mice to levels seen in healthy mice.
Rolipram has been tested before in mice, and was shown to improve memory. But the new research shows a previously unknown function of the drug that produces a physical change in the proteasome and increases its activity.
“We have uncovered a mechanism by which we can activate proteasomes,” said Dr. Myeku. “However, we still don’t have a full picture how those changes cause proteasomes to become super proteasomes that are able to remove toxic proteins from the brain. For now, it’s exciting to know that brain proteasomes can be repaired, which will allow us to develop better drugs.”
Drugs that target proteasomes in this way should work for any neurodegenerative disease caused by the accumulation of abnormal proteins, including Alzheimer’s, frontotemporal degeneration, Huntington’s, and Parkinson’s.
Dr. Duff noted, “Even though much work has been done, we still don’t know exactly which form of a particular protein is toxic to the brain. This has made it difficult to develop drugs to treat neurodegenerative diseases. In Alzheimer’s disease, the problem is compounded because several types of abnormal protein can accumulate in a person’s brain, including amyloid, tau, alpha-synuclein, and TDP43. We think that a well-functioning proteasome will be able to clear out everything at once.”
“This exciting research from Dr. Duff’s team advances our basic understanding of the proteasome system, provides a way to repair the system when it breaks, and holds the potential to alleviate symptoms of neurodegenerative disorders,” said Rod Corriveau, PhD, program director at the National Institute of Health’s National Institute of Neurological Disorders and Stroke, which provided funding for the study.
About the paper:
The study is titled, “Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling.” The other contributors are: Catherine L. Clelland (CUMC), Sheina Emrani (CUMC), Nikolay V. Kukushkin (Harvard Medical School), Wai Haung Yu (CUMC) and Alfred L. Goldberg (Harvard Medical School).
The study was supported by grants from the National Institute of Neurological Disorders and Stroke (NS074593), the CurePSP Foundation, the National Institute of General Medical Sciences (GM051923), the Fidelity Biosciences Research Initiative, and the Multiple Myeloma Research Foundation.

The researchers declare no financial or other conflicts of interest.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.

 

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

Well shit, what stroke protocol is your doctor following to make sure this is not a result after your stroke? ANYTHING AT ALL?
Has your doctor/hospital done anything since these earlier research results?
Your 33% dementia chance post-stroke from an Australian study?  May 2012.
Then this study came out and seems to have a range from 17-66%. December 2013.
A 20% chance in this research.   July 2013.
http://medicalxpress.com/news/2015-01-scientists-heart-disease-clues-alzheimer.html

You're screwed because your doctor has done nothing. Ask and you shall find out how pathetic your doctor and hospital are. Maybe you need your brain garbage disposal system jump started.

dgnews.docguide.com/alzheimer-s-plaques-found-middle-aged-people-brain-injuries?
People with brain injuries following head trauma may have build-up of the plaques related to Alzheimer’s disease in their brains, according to a study published in the February 3, 2016, online issue 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%. The editorial also says an estimated 3 to 5 million Americans live with a TBI-related disability.
“The study is small and the findings preliminary; however, we did find an increased build-up of amyloid plaques in people who had previously sustained a traumatic brain injury,” said David Sharp, MD, Imperial College London, London, United Kingdom.
“The areas of the brain affected by plaques overlapped those areas affected in Alzheimer’s disease, but other areas were involved,” he said. “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, 9 people with an average age of 44 years who had a single moderate to severe TBI had positron emission tomography (PET) and magnetic resonance imaging (MRI) brain scans. 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.
The brain injuries occurred between 11 months and up to 17 years before the start of the study. The participants were compared with 10 people with Alzheimer’s disease and 9 healthy participants.
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,” said Dr. Sharp. “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 Dr. Sharp.
SOURCE: American Academy of Neurology

When brain’s trash collectors fall down on the job, neurodegeneration risk picks up

Are they working overtime after a stroke? And if so are they getting rid of neurons that might be salvageable? When will your doctor know the answer?
And this might help your doctor answer the question.

Spring cleaning in your brain: U-M stem cell research shows how important it is

 

The trash collectors here;

http://scopeblog.stanford.edu/2013/09/04/when-brains-trash-collectors-fall-down-on-the-job-neurodeneration-risk-picks-up/