Combined therapy of focused ultrasound and aducanumab induces neurogenesis and decreases of beta-amyloid plaques in a mouse model of Alzheimer’s disease

20 pages for your doctor to apply for preventing your likely Alzheimers and better stroke recovery.

Combined therapy of focused ultrasound and aducanumab induces neurogenesis and decreases of beta-amyloid plaques in a mouse model of Alzheimers disease

Directed by Professor Jin Woo Chang Doctoral Dissertation submitted to the Department of Medicine, the Graduate School of Yonsei University in partial fulfillment of the requirements for the degree of Doctor of Philosophy Chanho Kong

'Game-changing' drug that could halt Alzheimer’s may be available in the US by March

Interesting that they don't tell you this is intravenous, once a month. From this earlier piece on it here:

Clinicians view new Alzheimer’s drug with guarded optimism

But is this the correct path to go down or should tau proteins be addressed? Is this just cleaning up existing plaque but not addressing new plaque being generated by tau? Cause and effect once again. Ask your doctor to clarify.

The real cause of Alzheimer’s is a dysfunctional ‘tau’ protein, a new study of over 3,600 brains finds.

 

The latest here:

'Game-changing' drug that could halt Alzheimer’s may be available in the US by March

An Alzheimer’s drug that could halt the progression of the disease has been hailed a “game changer”.

The memory-robbing disorder has no cure, with existing treatments working to ease its symptoms.

In severe cases, patients may become aggressive, struggle to move or even hallucinate.

Hopes have been raised after the US Food and Drug Administration (FDA) granted the medication aducanumab fast-track approval.

Read more: Gum disease linked to double the risk of dementia

Trials have demonstrated aducanumab helps to untangle Alzheimer’s tell-tale protein clumps in the brain, potentially reversing the disease.

The FDA has not considered a new treatment for the condition in 17 years, with aducanumab’s fate being decided by 7 March 2021.

If licensed, it would be the first therapy approved to delay Alzheimer’s progression.

Existing Alzheimer's drugs work to ease symptoms. (Getty Images)

‘A new era for Alzheimer’s treatments’

“The FDA’s acceptance of the aducanumab with priority review is an important step in the path to potentially having a treatment that meaningfully changes the course of Alzheimer’s disease,” said Michel Vounatsos, CEO of the manufacturer Biogen, as reported by Global News Wire.

“We believe aducanumab marks the beginning of a new era of potential treatments for Alzheimer’s disease that will inspire even more discovery and innovation to bring hope to those affected by this devastating disease.”

Read more: 'Game changing' Alzheimer's blood test edges closer

More than 5 million people in the US have Alzheimer’s, which is expected to increase to over 13 million by 2050.

In the UK, around 850,000 people have dementia – the umbrella term for conditions that cause a gradual decline in brain function.

Alzheimer’s is the most common type of dementia, affecting between 50% and 75% of patients in the UK.

The disease is thought to be caused by the abnormal build-up of proteins in and around brain cells.

Two of these are amyloid – which forms plaques, and tau – which develops into tangles.

Over time, the chemical messengers that send signals between brain cells decline.

Different areas of the vital organ then shrink, usually starting with those responsible for memories.

Trials have shown aducanumab works to untangle these clumps, slowing memory loss.

The drug was also linked to improvement in a patient’s ability to carry out day-to-day tasks, like household chores and leaving the home alone.

Read more: Elderly who distinctly smell roses 'have half the risk of dementia'

“I am heartened by what this progress may mean for people living with Alzheimer’s disease and their families,” said Dr Christopher van Dyck, from the Yale Alzheimer’s Disease Research Center.

“If aducanumab is determined to be effective in reducing the decline in cognition and activities of daily living resulting from progression of this disease by addressing the underlying disease pathology, it will deliver meaningful benefits to those who most need them.”

Keeps patients ‘in a better place for a longer time’

Aducanumab has had a bumpy road. Studies were scrapped in March 2019 after two late-stage trials suggested it was of no benefit.

Several months later, Biogen looked at a larger amount of data that became available after the trials stopped.

It found the drugs were effective providing they were given early enough and at a sufficient dose.

Experts hope aducanumab will benefit those with early signs of dementia, helping to halt or slow the disease before patients became incapacitated.

The FDA has been set an “action date” of 7 March 2021, but “plans to act early on this application under an expedited review”.

Michael Yee, an analyst at the investment bank Jefferies, expects a verdict in the first quarter of 2021, adding the data demonstrating the drug’s effectiveness is “mixed and still inconclusive”, Fierce Biotech reported.

Nevertheless, the fast-track approval suggests the FDA is “comfortable with the totality of the data, recognises high unmet need and really wants to get an Alzheimer’s drug approved”, he added.

Analyst Brian Abrahams, from RBC Capital Markets, has given aducanumab a 30% chance of approval.

Dr Dennis Selkoe from Harvard told wbur: “I think there’s a reasonable chance that aducanumab, if approved and we don’t know that yet, will be the first disease-modifying agent for Alzheimer’s, and that will be a huge milestone, and patients of mine and others can access the drug.

“Having cared for hundreds of patients with this disease, this would be a game changer.

“At least for some of my patients, if aducanumab is approved, [it would be] something that will slow down their deterioration, that will keep them in a better place for a longer time.”

The FDA only accepts drugs for priority review if they offer major advances in treatments or provide a therapy where none existed.

If approved in the US, experts are confident other health watchdogs around the world will consider doing the same.

In the meantime, Biogen is planning further studies, which will offer high doses to all eligible participants from the earlier trials.

 

Antibody Reduces Harmful Brain Amyloid Plaques in Alzheimer's Patients

But is this the correct path to go down or should tau proteins be addressed? Is this just cleaning up existing plaque but not addressing new plaque being generated by tau? Cause and effect once again.

The real cause of Alzheimer’s is a dysfunctional ‘tau’ protein, a new study of over 3,600 brains finds.

Antibody Reduces Harmful Brain Amyloid Plaques in Alzheimer's Patients 

Aducanumab, an antibody developed by the University of Zurich, has been shown to trigger a meaningful reduction of harmful beta-amyloid plaques in patients with early-stage Alzheimer's disease. These protein deposits in the brain are a classic sign of Alzheimer's disease and contribute to the progressive degeneration of brain cells. The researchers furthermore demonstrated in an early stage clinical study that, after one year of treatment with Aducanumab, cognitive decline could be significantly slowed in antibody-treated patients as opposed to the placebo group.
Although the causes of Alzheimer's disease are still unknown, it is clear that the disease commences with progressive amyloid deposition in the brains of affected persons between ten and fifteen years before the emergence of initial clinical symptoms such as memory loss. Researchers have now been able to show that Aducanumab, a human monoclonal antibody, selectively binds brain amyloid plaques, thus enabling microglial cells to remove the plaques. A one-year treatment with the antibody, as part of a phase Ib study, resulted in almost complete clearance of the brain amyloid plaques in the study group patients. The results, which were realized by researchers at UZH together with the biotech company “Biogen” and the UZH spin-off “Neurimmune,” have been published in the renowned science journal “Nature.”
Reduction of brain amyloid plaque is dependent on treatment duration and dosage
“The results of this clinical study make us optimistic that we can potentially make a great step forward in treating Alzheimer's disease,” says Roger M. Nitsch, professor at the Institute for Regenerative Medicine at UZH. “The effect of the antibody is very impressive. And the outcome is dependent on the dosage and length of treatment.” After one year of treatment, practically no beta-amyloid plaques could be detected in the patients who received the highest dose of the antibody.
The antibody was developed with the help of a technology platform from “Neurimmune.” Using blood collected from elderly persons aged up to one hundred and demonstrating no cognitive impairment, the researchers isolated precisely those immune cells whose antibodies are able to identify toxic beta-amyloid plaques but not the amyloid precursor protein that is present throughout the human body and that presumably plays an important role in the growth of nerve cells. The good safety profile of Aducanumab in patients may well be attributed to the antibody’s specific capacity to bond with the abnormally folded beta-amyloid protein fragment as well as the fact that the antibody is of human origin.
Investigational treatment also curbs cognitive decline
165 patients with early-stage Alzheimer's disease were treated in the phase 1b clinical trial. Although not initially planned as a primary study objective, the good results encouraged researchers to additionally investigate how the treatment affected the symptoms of disease. This was evaluated via standardized questionnaires to assess the cognitive abilities and everyday activities of the patients. “Aducanumab also showed positive effects on clinical symptoms," is how Nitsch sums up the findings. “While patients in the placebo group exhibited significant cognitive decline, cognitive ability remained distinctly more stable in patients receiving the antibody.”
Some of the trial participants temporarily suffered from amyloid-related imaging abnormality (ARIA), an adverse effect that can be detected via magnetic resonance imaging. In a minority of cases, this was accompanied by temporary mild to moderate headaches. The UZH researchers believe that ARIA is a measurable biological effect of amyloid clearance.
The promising effects of Aducanumab are currently being investigated in two large phase three clinical studies to further evaluate safety and efficacy. Involving over 300 centers in 20 countries throughout North America, Europe, and Asia, these studies are evaluating the effectiveness and safety of the antibody on a total of 2,700 patients with early-stage Alzheimer's disease.
http://www.media.uzh.ch/en/Press-Releases/2016/alzheimer-aducanumab.html

• Full bibliographic informationJeff Sevigny, Ping Chiao, Thierry Bussière, Paul H. Weinreb, Leslie Williams, Marcel Maier, Robert Dunstan, Stephen Salloway, Tianle Chen, Yan Ling, John O’Gorman, Fang Qian, Mahin Arastu, Mingwei Li, Sowmya Chollate, Melanie S. Brennan, Omar Quintero-Monzon, Robert H. Scannevin, H. Moore Arnold, Thomas Engber, Kenneth Rhodes, James Ferrero, Yaming Hang, Alvydas Mikulskis, Jan Grimm, Christoph Hock, Roger M. Nitsch & Alfred Sandrock.
  The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease.
  Nature. September 1, 2016. doi:10.1038/nature19323

Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

I bet no matter what scientific proof is given our legislators will not remove marijuana from Schedule I classification. States will have to do it and drag our federal government kicking and screaming into a new world. Stroke survivors will likely need this due to our increased chances of getting dementia/Alzheimers.
http://medicalxpress.com/news/2016-06-cannabinoids-plaque-forming-alzheimer-proteins-brain.html
Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer's disease.

While these exploratory studies were conducted in neurons grown in the laboratory, they may offer insight into the role of inflammation in Alzheimer's disease and could provide clues to developing novel therapeutics for the disorder.
"Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer's, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells," says Salk Professor David Schubert, the senior author of the paper.
Alzheimer's disease is a progressive brain disorder that leads to memory loss and can seriously impair a person's ability to carry out daily tasks. It affects more than five million Americans according to the National Institutes of Health, and is a leading cause of death. It is also the most common cause of dementia and its incidence is expected to triple during the next 50 years.
It has long been known that amyloid beta accumulates within the nerve cells of the aging brain well before the appearance of Alzheimer's disease symptoms and plaques. Amyloid beta is a major component of the plaque deposits that are a hallmark of the disease. But the precise role of amyloid beta and the plaques it forms in the disease process remains unclear.
In a manuscript published in June 2016's Aging and Mechanisms of Disease, Salk team studied nerve cells altered to produce high levels of amyloid beta to mimic aspects of Alzheimer's disease.
The researchers found that high levels of amyloid beta were associated with cellular inflammation and higher rates of neuron death. They demonstrated that exposing the cells to THC reduced amyloid beta protein levels and eliminated the inflammatory response from the nerve cells caused by the protein, thereby allowing the nerve cells to survive.
"Inflammation within the brain is a major component of the damage associated with Alzheimer's disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves," says Antonio Currais, a postdoctoral researcher in Schubert's laboratory and first author of the paper. "When we were able to identify the molecular basis of the inflammatory response to amyloid beta, it became clear that THC-like compounds that the nerve cells make themselves may be involved in protecting the cells from dying."
Brain cells have switches known as receptors that can be activated by endocannabinoids, a class of lipid molecules made by the body that are used for intercellular signaling in the brain. The psychoactive effects of marijuana are caused by THC, a molecule similar in activity to endocannabinoids that can activate the same receptors. Physical activity results in the production of endocannabinoids and some studies have shown that exercise may slow the progression of Alzheimer's disease.
Schubert emphasized that his team's findings were conducted in exploratory laboratory models, and that the use of THC-like compounds as a therapy would need to be tested in clinical trials.
In separate but related research, his lab found an Alzheimer's drug candidate called J147 that also removes amyloid beta from nerve cells and reduces the inflammatory response in both nerve cells and the brain. It was the study of J147 that led the scientists to discover that endocannabinoids are involved in the removal of amyloid beta and the reduction of inflammation.

Explore further: Alzheimer protein's structure may explain its toxicity

More information: Antonio Currais et al. Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids, npj Aging and Mechanisms of Disease (2016). DOI: 10.1038/npjamd.2016.12

Light Improves Alzheimer's in More Ways than One

Would this help stroke survivors? This fuckingly simple question will NEVER be answered since we have NO stroke leadership or strategy.
http://www.alzheimersweekly.com/2014/06/light-improves-alzheimers-in-more-ways.html
A down-to-earth Alzheimer's trial provided 4 weeks of tailored light therapy. The therapy significantly increased sleep quality, efficiency and total sleep duration. Daytime light therapy also significantly reduced rates of depression and agitation. Learn how.

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A study offering an easy-to-do conclusion suggests that light treatment, tailored to increase circadian stimulation during the day, may improve sleep, depression and agitation in people with Alzheimer's and related dementia.  And since sleep clears

More at link.

How Sleep Clears Alzheimer's

What is your sleep protocol from your doctor?
http://www.alzheimersweekly.com/2015/09/how-sleep-clears-alzheimers.html
Beta-amyloid (also known as "plaque") is the main suspect behind Alzheimer's. In the lab, it disappeared twice as quickly during sleep. Find out how sleep doubles the clearance of this dangerous Alzheimer's-causing molecule.

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A mouse study suggests that sleep helps restore the brain by flushing out toxins that build up during waking hours. The results point to a potential new role for sleep in health and disease.

More at link.

New Alzheimer’s treatment fully restores memory function

Lucky if you are a mouse with Alzheimers.
http://www.sciencealert.com/new-alzheimer-s-treatment-fully-restores-memory-function

Australian researchers have come up with a non-invasive ultrasound technology that clears the brain of neurotoxic amyloid plaques - structures that are responsible for memory loss and a decline in cognitive function in Alzheimer’s patients.
If a person has Alzheimer’s disease, it’s usually the result of a build-up of two types of lesions - amyloid plaques, and neurofibrillary tangles. Amyloid plaques sit between the neurons and end up as dense clusters of beta-amyloid molecules, a sticky type of protein that clumps together and forms plaques.
Neurofibrillary tangles are found inside the neurons of the brain, and they’re caused by defective tau proteins that clump up into a thick, insoluble mass. This causes tiny filaments called microtubules to get all twisted, which disrupts the transportation of essential materials such as nutrients and organelles along them, just like when you twist up the vacuum cleaner tube.
As we don’t have any kind of vaccine or preventative measure for Alzheimer’s - a disease that affects 343,000 people in Australia, and 50 million worldwide - it’s been a race to figure out how best to treat it, starting with how to clear the build-up of defective beta-amyloid and tau proteins from a patient’s brain. Now a team from the Queensland Brain Institute (QBI) at the University of Queensland have come up with a pretty promising solution for removing the former.
Publishing in Science Translational Medicine, the team describes the technique as using a particular type of ultrasound called a focused therapeutic ultrasound, which non-invasively beams sound waves into the brain tissue. By oscillating super-fast, these sound waves are able to gently open up the blood-brain barrier, which is a layer that protects the brain against bacteria, and stimulate the brain’s microglial cells to activate. Microglila cells are basically waste-removal cells, so they’re able to clear out the toxic beta-amyloid clumps that are responsible for the worst symptoms of Alzheimer’s.
The team reports fully restoring the memory function of 75 percent of the mice they tested it on, with zero damage to the surrounding brain tissue. They found that the treated mice displayed improved performance in three memory tasks - a maze, a test to get them to recognise new objects, and one to get them to remember the places they should avoid.
"We’re extremely excited by this innovation of treating Alzheimer’s without using drug therapeutics," one of the team, Jürgen Götz, said in a press release. "The word ‘breakthrough’ is often misused, but in this case I think this really does fundamentally change our understanding of how to treat this disease, and I foresee a great future for this approach."
The team says they’re planning on starting trials with higher animal models, such as sheep, and hope to get their human trials underway in 2017. 
You can hear an ABC radio interview with the team here.