Brain Cells With Alzheimer’s Disease Grown in a Petri Dish

By Carl Engelking | October 17, 2014 3:24 pm

petri dish

There’s a new tool for researchers in pursuit of a cure for Alzheimer’s disease: lab-grown brains.

For the first time, neuroscientists from Massachusetts General Hospital have grown functioning human brain cells that develop Alzheimer’s disease in a petri dish. The breakthrough offers researchers a new method to test cures and decipher the origins of the disease.

Dishing up Alzheimer’s

To be clear, a fully functioning brain is not what’s grown in the lab. Rather, what results is a culture of neurons behaving like they would in the brain.

The process begins with human embryonic stem cells, which can transform into any cell within the body. Researchers grew the stem cells in an electrically charged mixture of chemicals and turned them into neurons. Then, they genetically engineered the neurons to express mutations associated with Alzheimer’s disease. Specifically, the neurons produced high levels of proteins called beta amyloids, which cause plaques and coils known as tangles to form — telltale signs of Alzheimer’s.

Researchers placed their homemade neurons into a petri dish filled with a gel. Within six weeks the neurons took root and grew into 3-D interconnecting webs like you’d find in the brain. More importantly, the cells formed plaques and tangles like someone with Alzheimer’s. Researchers published their findings this week in the journal Nature.

Taking on Alzheimer’s

Data and observations gleaned from the lab-grown neurons gave credence to a debated theory that the accumulation of beta amyloids gives Alzheimer’s its start. Researchers believe inhibiting enzyme that triggers production of beta amyloids could be a therapeutic target. Secondly, producing petri dish brains serves as a safe and ethical way to test experimental drugs on human brain cells.

“It is a giant step forward for the field,” said Dr. P. Murali Doraiswamy, an Alzheimer’s researcher at Duke University told the New York Times. “It could dramatically accelerate testing of new drug candidates.”

Roughly 5.2 million people in the United States have Alzheimer’s, and millions more are in some way touched by the disease through friends and relatives. Perhaps a cure will someday be found in a petri dish right beneath our noses.

 

Photo credit: /Shutterstock 

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  • Lane Simonian

    The primary cause of Alzheimer’s disease is neither tau tangles nor amyloid but peroxynitrites. Peroxynitrites increase the beta secretase which leads to the c-terminal fragment of the amyloid precursor protein (the gamma secretase then leads to the formation of amyloid oligomers and plaques). So if you scavenge peroxynitrites, you not only inhibit beta secretase, you stop and partially reverse the damage that peroxynitrites do to the brain. This damage includes reduced blood flow in the brain, the hyperphosporylation and nitration of tau proteins which limits neurotransmissions, the reduced synthesis and release of neurotransmitters involved in short-term memory, sleep, social recognition, mood, and alertness, delusions and sometimes hallucinations, the end to neuron regeneration in the hippocampus, and the death of brain cells.

    The best peroxynitrite scavengers are methoxyphenols and these compounds have partially reversed Alzheimer’s disease in human clinical trials. These compounds include eugenol in rosemary essential oil via aromatherapy (Jimbo, 2009), eugenol and ferulic acid in lemon balm (Melissa officinalis) extract (Akhondzadeh, 2004), and ferulic acid and syringic acid in panax ginseng (Heo 2011 and 2012).

    We are close to having effective treatments for Alzheimer’s disease but a major shift in the understanding of what causes the disease has to occur in the mainstream Alzheimer’s community; namely from tau tangles and amyloid to peroxynitrites.

    • Dennis R.

      @Lane – While there may or may not be something to the peroxynitrites hypothesis for Alzheimer’s, the point of the article was that there is now a new and ethical tool for testing potential treatments on human brain cells that are expressing mutations that have been shown to be causative of Alzheimer’s Disease. This is a great development. Get off your high horse for a minute and just appreciate this big step that the good researchers at Mass General have done for the rest of us.
      BTW, aromatherapy, really? You know this is a science blog, right?

      • Lane Simonian

        The problems is asserting causation where none has been proven. The fact that genetic mutations that cause early onset Alzheimer’s disease also lead to amyloid and neurofibrillary tangles does not advance our understanding of Alzheimer’s disease. The death of neurons can and does occur without either amyloid or neurofibrillary tangles. So inhibiting the development of amyloid or neurofibrillary tangles will not help unless you also inhibit peroxynitrites. You can go through hundreds of drugs using this model that inhibit gamma and beta secretases and unless you are lucky to find one that is a peroxynitrite scavenger, they will not work well in human beings.

        We already know which compounds are peroxynitrite scavengers. One example is eugenol in various essential oils.

        In Vitro Activity of the Essential Oil of Cinnamomum zeylanicum and Eugenol in Peroxynitrite-Induced Oxidative Processes

        Effects of Eugenol on the Central Nervous System: Its Possible Application to Treatment of Alzheimer’s Disease, Depression, and Parkinson’s Disease

        The essential oils used in aromatherapy in the following study were rosemary containing eugenol and lemon containing geraniol for cognition and orange and lavender containing linalool to reduce anxiety.

        Effect of aromatherapy on patients with Alzheimer’s disease.

        RESULTS: All patients showed significant improvement in personal orientation related to cognitive function on both the GBSS-J and TDAS after therapy. In particular, patients with AD showed significant improvement in total TDAS scores. Result of routine laboratory tests showed no significant changes, suggesting that there were no side-effects associated with the use of aromatherapy. Results from Zarit’s score showed no significant changes, suggesting that caregivers had no effect on the improved patient scores seen in the other tests.

        CONCLUSIONS:

        In conclusion, we found aromatherapy an efficacious non-pharmacological therapy for dementia. Aromatherapy may have some potential for improving cognitive function, especially in AD patients.

        Most U.S. scientists are taught early in their careers that aromatherapy is a pseudoscience and no amount of studies showing the chemical properties of the compounds in the essential oils and their effect on pathways in the human brain will ever change this engrained opinion. This is unfortunate.

        I am not on a high horse; I am just suggesting several reporters claimed more than was actually there. I don’t deny it was technically brilliant, just not a breakthrough in regards to our understanding of how Alzheimer’s disease works and how to most effectively treat the disease.

    • Charles Sangston

      Please see literature related to vitamin D, curcumin, and neuro benefit.

  • http://www.mazepath.com/uncleal/qz4.htm Uncle Al

    electrically charged mixture of chemicals” Amusing.

    Geronological research based on a large affluent elderly population Laguna Hills, CA ex Leisure World) demonstrates classical anatomical pathology and external loss of function are not well correlated.

  • dickG

    Why, what’s so new about this?
    Dr. Frankenstein discovered this years ago!
    .

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