MIT neuroscientist use lab-engineered blood-brain barrier to make breakthrough in understanding Alzheimer's

Neuroscientists at the Massachusetts Institute of Technology (MIT) may have made a breakthrough in understanding Alzheimer’s, involving a molecular pathway for which there are already medicines approved by the Food and Drug Administration that can suppress it.

Scientists were able to determine how the APOE gene – a gene present in approximately 25% of the general population and in almost all Alzheimer’s victims – prevents the brain from receiving needed nutrients from the blood, MIT News reported. From that knowledge, they could then determine what medications would counteract the effect.

To make the finding, researchers at MIT’s Picower Institute for Learning and Memory had to first construct a lab-engineered model of the blood-brain barrier that, under normal conditions, permits nutrients and oxygen to pass into the brain from the blood stream.

In a study recently published in “Nature Medicine,” Li-Huei Tsai, Picower Professor of Neuroscience and director of the Picower Institute, pointed to increased production of a protein related to the gene variant found in most Alzheimer’s patients.

The molecular pathway that is affected has existing medications for suppressing it, MIT News reported. Those medications are currently used to suppress the immune system response in transplant victims.

The researchers were also able to show that the elevated protein level they were able to mitigate with the medications in their lab-engineered specimens is present in the prefrontal cortex and hippocampus of those with the gene variant. Those regions are significantly affected by Alzheiner’s.

“That is a salient point of this paper,” Tsai, a founding member of MIT’s Aging Brain Initiative, told MIT News. “It’s really cool because it stresses the cell-type specific function of APOE.”

But Tsai and study lead author Joel Blanchard, a postdoc in Tsai’s lab, told MIT news the potential side effects of medication used to suppress immune system response does mean that further research is needed.

“Instead, it points toward the value of understanding the mechanism,” Blanchard told MIT News. “It allows one to design a small molecule screen to find more potent drugs that have less off-target effects.”