In a 2014 interview with The New York Times, Dr. Murali Doraiswamy of Duke University went on the record stating that “the lack of a viable model for Alzheimer’s disease has been the Achilles’ heel of the field.” This quote was featured in an article discussing the breakthrough research from Drs. Tanzi and Kim pioneering Alzheimer’s-In-A-Dish. In the field of neurodegeneration, there continues to be tremendous interest in addressing this Achilles’ heel by developing a model system that recapitulates aspects of the physiology of the human brain.

Since the publication of the New York Times article, Breakthrough Replicates Human Brain Cells for Use in Alzheimer’s Research, the models have become even more effective at mimicking aspects of the human brain. Since then, the research team has developed new innovations to make the 3D model even more effective at replicating a brain with Alzheimer’s disease by including immune system cells.

This most recent version adds another key element to the equation: the inclusion of the blood-brain barrier, which provides for the entry and exit of both good and harmful particles into and out of the brain. The new enhancements with Alzheimer’s-In-A-Dish provide for targeted screening of existing drugs that could improve blood-brain barrier function or prevent the cognitive impairments associated with the accumulation of plaques and tangles.

In Alzheimer’s disease, the blood-brain barrier has been shown to deteriorate before there is evidence of cognitive decline. During healthy aging, harmful materials in the blood are prevented from entering the brain by a blood-brain barrier that functions properly; the degradation of the blood-brain barrier is associated with many neurological diseases. With Alzheimer’s disease, specific impairments in the blood-brain barrier system have been well-documented and include:

• increased permeability allowing for unwanted particles to gain access to the brain
• decreased expression of key adhesion molecules that help cells bind with one another, which is important to the transfer of debris from the brain to the blood system for transport out of the body
• the build-up of amyloid plaques in the cells that line blood vessels

Researchers are now able to observe how the blood-brain barrier degrades in Alzheimer’s disease and are using this information to identify potential key druggable targets.

The research was highlighted by the MIT press office in a piece titled, “Tissue model reveals role of blood-brain barrier in Alzheimer’s.”

http://news.mit.edu/2019/alzheimers-model-blood-brain-0812

The original Alzheimer’s-in-a-Dish feature in The New York Times from 2014 is available at the following link: https://www.nytimes.com/2014/10/13/science/researchers-replicate-alzheimers-brain-cells-in-a-petri-dish.html

To learn more about the engineering involved in this 3D model, the original paper is available through Science Advances: https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.201900962