Keeping Aging Brains Healthy

“We wanted to know if we could distinguish whether each cell type has differential gene expression patterns between healthy and diseased brain tissue,” said Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory. “This is the power of single-cell-level analysis: You have the resolution to really see the differences among all the different cell types in the brain.” The most surprising finding, the researchers say, was the discovery of a dramatic difference between brain cells from male and female Alzheimer’s patients.

APOE4 is three times more common among Alzheimer’s patients than it is among the general population, which has the common form of the gene, APOE3. Researchers found that APOE4 promotes the accumulation of the beta amyloid proteins that cause the characteristic plaques seen in the brains of Alzheimer’s patients. The researchers also found that they could eliminate the signs of Alzheimer’s in brain cells with APOE4 by editing the gene with CRISPR to turn it into the APOE3 variant.

In a study of mice with symptoms that mimic early Alzheimer’s disease, researchers found that while the mice had trouble recalling memories, those memories still existed and could be optogenetically retrieved for up to eight days. This study suggests that re-activating certain synapses could help restore some memory recall function in patients with early stage Alzheimer’s disease.

MIT researchers have developed a way to make extremely high-resolution images of tissue samples, at a fraction of the cost of other techniques that offer similar resolution. The resolution allows scientists to see the proteins that cluster together in complex patterns at brain synapses, helping neurons to communicate with each other.

With 40-hertz light therapy, Alzheimer’s patients may one day be able to treat themselves—perhaps wearing a special headset that emits the flickering light. Here, we see a slice of a mouse brain exposed to light therapy causing a reversal of severe neurodegeneration.