How a 3D Model of Alzheimer’s Disease is Providing New Hope in the Search for Treatments

Reigning in Alzheimer’s disease continues to be a challenge — more than 10 million families are affected by this degenerative neurological disease, and the number of patients dying from the disease has increased 68 percent since 2010.

In the past decade, attempts at developing drugs to slow or halt the progression of Alzheimer’s disease have been unsuccessful. The traditional path for early testing of promising therapies – mouse models – has been ineffective, and more than a dozen major clinical trials have failed.

But scientists and clinicians at Massachusetts General Hospital’s Institute for Neurodegenerative Disease (MIND) have developed an innovative new approach that could significantly improve the drug development process.  The laboratory teams of Doo Yeon Kim, PhD, an investigator in the Genetics and Aging Research Unit at MIND, and Rudy Tanzi, PhD, have found a way to grow human neural stem cells in a three-dimensional gel matrix.

This gel system allows the neural cells to grow more naturally and form into 3-D networks just like they do in the brain. It also provides a more accurate model of the signature plaques and tangles that develop around these neurons in Alzheimer’s disease.

The stem cells used in this lab model are genetically engineered to produce two proteins that are the hallmarks of Alzheimer’s disease – β-amyloid and tau. In the brains of people with Alzheimer’s, excessive accumulation of β-amyloid results in the formation of plaques in the spaces between neural cells, while tau is the main component of destructive neurofibrillary tangles within the cells.

Until Dr. Kim’s success, no single model of Alzheimer’s disease contained both amyloid plaques and neurofibrillary tangles. It usually takes a year to develop plaques in mouse models, it took only six weeks to develop both plaques and tangles in the “dish.”

Dr. Kim is now working with a consortium of labs to test thousands of FDA-approved drugs in this “Alzheimer’s in a dish” model to see if any of the drugs are effective in reducing levels of p-tau, a protein that is increased in Alzheimer’s patients.

Of the 2,400 drugs that have been tested, the team had approximately 40 promising hits that they can now investigate further.

Learn more:

Researchers and Clinicians Revolutionize Prevention Efforts for Brain Disease

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What if you had a strong family history of Alzheimer’s disease, but weren’t currently showing any symptoms? What could you do to stave off the cognitive decline and loss of memory associated with this devastating disease? A team of researchers and clinicians at Massachusetts General Hospital wants to be your resource in situations like these.

The Institute for Brain Health at Mass General is revolutionizing the way we treat brain disease by developing new strategies for prevention, risk reduction and early treatment. They work with individuals who are at high genetic risk for brain diseases as well as healthy individuals who want to maintain good brain function as they age.

The Institute encourages life-long relationships with its patients to support the establishment of healthy brain habits and to provide guidance when new illnesses develop that can impact the brain. In doing so, the research team is able to collect longitudinal data about the development and progression of brain diseases throughout the life cycle. This data is helping to advance understanding about the progression of diseases like Alzheimer’s, in which so much is still unknown.

Learn more about the Institute for Brain Health in this article.

The Research Institute:
Saving Lives Through Science

The Massachusetts General Hospital Research Institute is the largest hospital-based research program in the United States, with a community of over 10,000 people working across more than 30 institutes, centers and departments.

Our researchers work side-by-side with physicians to pioneer the latest scientific advancements for curing disease and healing patients in Boston, across the United States and around the world.

To learn more about the Research Institute, please visit our website.

Both Patients and Researchers Have a Role to Play in Preserving Brain Function

Reposted from the Mass General Giving Website

green-braintreeBrain health is key to living a long and happy life.

Too many Americans suffer from Alzheimer’s and other brain conditions that rob them of their memories, their independence and their lives. In fact, 1 of every 3 seniors dies due to Alzheimer’s and other forms of dementia.

Here are some tips for improving brain health:

First, exercise is essential.

Promoting blood flow to the brain is vitally important, so exercise is a key part of maintaining brain health. Keeping your heart pumping provides the vital oxygen your brain requires to stay active.

Second, be social.

Those who have social networks maintain healthier brains than those who are isolated. So, visit with your friends, family and neighbors. Seek out social occasions and fight back against isolation.

Third, maintain a healthy balance.

Focus upon a diet that is high in fiber and fruit, be sure to get at least 7 to 8 hours of sleep each night, and avoid stress as much as possible.

An active brain is more likely to stay a healthy brain. You must constantly challenge your brain.

Fourth, use it or lose it.

An active brain is more likely to stay a healthy brain. You must constantly challenge your brain. Puzzles alone are not enough. Learn new things. Constantly educate your mind, because learning results in positive, physical changes in our brain.


Mass General created the Institute for Brain Health to integrate our research into Alzheimer’s, strokes, Parkinson’s, ALS and other brain-related diseases and conditions that affect too many Americans. The doctors and staff are working to develop new treatments to preserve brain function and prevent these diseases.

The Institute’s co-founder Jonathan Rosand, MD, MSc, chief of the Division of Neurocritical Care and Emergency Neurology, has led groundbreaking research into preventing brain disease, and Bradford Dickerson, MD, director of Clinical Applications, is studying older adults who have maintained the resilient minds of younger people.

While our researchers do their job to fight brain diseases, please do your part to protect your brain by keeping it active. Check out our Brain Health Quiz, learn something new and keep your brain healthy today.

For Alzheimer’s Patients, Every Day is the Longest Day

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June 21st is not only the longest day of the calendar year, but it is also a special day focused on Alzheimer’s disease (AD), an irreversible progressive form of dementia that slowly destroys memory and thinking skills.

The challenges of living with AD make each day the “longest” in terms of sheer survival. The Longest Day is meant to pay tribute to those suffering from AD and their loved ones and caregivers; to raise awareness of the challenges that come with a diagnosis of AD; and to raise funds for continued AD research.

Today an estimated 5 million Americans have AD. With that figure expected to quadruple in the next 30 years, there’s a growing need to find a way to prevent or stop progression of this devastating disease.

Massachusetts General Hospital researchers are hard at work trying to learn more about the disease. Here are a few examples of their recent discoveries:

  • Abnormal accumulation of tau and amyloid beta proteins in the human brain are two characteristics of AD. In a recent study using advanced imaging techniques, lead author Jorge Sepulcre, MD, PHD, of the Gordon Center for Medical Imaging, looked at the distribution of tau and amyloid beta deposits in the brains of elderly, cognitively normal individuals. Read how the clues his team found about the spreading pathways of AD could help researchers one day identify a specific target to try and stop the disease’s progression.
  • Could the development of amyloid beta plaques in the brain be a response to infection? Mass General researchers Rudy Tanzi and Robert Moir are investigating amyloid beta’s role in the body. Their findings could possibly open new fronts for treating or preventing AD by attacking infection before plaques begin to form.
  • New research from the Mass General Epilepsy Service suggests a potential connection between the devastating memory loss associated with AD and “silent” seizures in the memory center of the brain. Learn how this discovery could lead to potential new treatment options for patients with AD.
  • If you are wondering about your risk of developing AD, the answer may be found right under your nose. A team from the Center for Alzheimer’s Research has developed a series of four tests designed to measure early indications of AD based on an individual’s ability to recognize, remember and distinguish among odors. Learn more about the tests.

Researchers Detect “Silent” Seizures in Alzheimer’s Patients

First let’s define a key word:
Hippocampus: The brain structure responsible for memory development. The hippocampus is a key part of the brain affected by Alzheimer’s disease, and also a common source of seizures in people with epilepsy.

New research from Massachusetts General Hospital suggests a potential new connection between the devastating memory loss associated with Alzheimer’s disease (AD) and “silent” seizures in the memory center of the brain.

The small study enrolled two female patients in their 60s with early AD and no known history of seizures. Because electrodes placed on the scalp are often unable to detect seizure activity deep in the brain, researchers surgically implanted electrodes on both sides of the brain through the foramen ovale (FO), a narrow opening at the base of the skull, in addition to scalp EEG. Each patient’s brain activity was monitored for 24 to 72 hours.

The FO electrodes recorded evidence of seizures in the hippocampuses of both patients, while the scalp EEG readings did not detect any abnormal electrical activity. Most notably, these seizures primarily occurred when patients were asleep, a critical time for memory consolidation.

“While it is not surprising to find dysfunction in brain networks in Alzheimer’s disease, our novel finding that networks involved in memory function can become silently epileptic could lead to opportunities to target that dysfunction with new or existing drugs to reduce symptoms or potentially alter the course of the disease,” says Andrew Cole, MD, Director of the Mass General Epilepsy Service and senior author of the Nature Medicine paper.

One patient received anti-seizure medicine as a treatment following the scan, which seemed to cut down on AD-linked symptoms such as confusion and repeating the same question. The other patient started on the medication but it had to be discontinued due to adverse effects on her mood.

A recent study led by Alice Lam, MD, PhD, also of the MGH Epilepsy Service and lead author of the current study, demonstrated a novel tool for detecting hippocampal seizures not detectible by scalp EEGs in patients with epilepsy. Cole and his team are working to refine this tool and apply it to AD.

Due to the small size of the study, further research is also needed to validate the results with a broader population.

Probe of Alzheimer’s Follows Paths of Infection

Rudy Tanzi (left) and Robert Moir. (photo credit: Jon Chase/Harvard Staff Photographer)

Could the development of amyloid beta plaques in the brain — a hallmark of Alzheimer’s disease — be a response to infection? Mass General researchers Rudy Tanzi and Robert Moir are investigating amyloid beta’s role in the body. Their findings could possibly open new fronts for treating or preventing Alzheimer’s disease by attacking infection before plaques begin to form.

You can read more about their research here.

Doctors Look To Prevent Alzheimer’s Disease Decades Before Symptoms or Diagnosis

Healthcare providers are focusing more on prevention, given recent discoveries into this degenerative neurological condition. Meanwhile, treatment and management remain challenging, as families and caregivers often struggle to find appropriate and affordable care.

Check out this interview from New Hampshire Public Radio which includes Massachusetts General Hospital cognitive neuroscientist and instructor of neurology, Jonathan Jackson, PhD.