Technique Devised for 3-D Alzheimer’s Brain Images

Rendering of three amyloid plaques (Fisher Center for Alzheimer’s Research Foundation)

14 July 2016. Researchers in New York applied an imaging technique that visualizes the build-up of amyloid-beta plaques in the brain associated with Alzheimer’s disease. The team from the lab of Rockefeller University neuroscientist Paul Greengard published its findings in today’s issue of the journal Cell Reports.

Alzheimer’s disease is progressive neurodegenerative disease affecting growing numbers of older people worldwide. People with Alzheimer’s disease often have deposits of abnormal substances in spaces between brain cells, known as amyloid-beta peptides, as well as misfolded tangles of proteins inside brain cells known as tau. Up to now, these accumulations in the brain were not clearly or precisely visualized, which can hamper diagnosis and treatment of Alzheimer’s disease.

The Rockefeller team, led by researcher Marc Flajolet and funded in part by the Fisher Center for Alzheimer’s Research, adapted a visualization method known as immunolabeling-enabled three-dimensional imaging of solvent-cleared organs, or iDisco, designed for large and high-volume tissue samples. The iDisco techniques, developed in a related Rockefeller lab, quickly and inexpensively labels characteristic antibodies associated with tissue, which enables the simultaneous color highlighting of different tissue types, including neurons and blood vessels, as well as build-ups of proteins such as amyloid-beta.

Flajolet and colleagues first used iDisco techniques to visualize brains of lab mice, up to 27 months in age, induced with Alzheimer’s disease. The researchers were able to identify amyloid-beta and tau accumulations in the mouse brains, as well as blood vessels and glial or immune-system cells in the brain. The team coupled their visualizations with automated detection, mapping, and quantification of plaque build-ups in the mice.

The team then applied iDisco methods to slices of frozen brains from deceased humans with Alzheimer’s disease. The researchers say the human samples needed no special preparation, and returned 3-D images showing as expected a more complex brain than those in mice. More importantly for understanding Alzheimer’s disease, the images revealed large 3-D amyloid patterns that the researchers believe can help establish different types or stages of Alzheimer’s disease.

“A better understanding of these plaques,” says Flajolet in a university statement, “as well as other key features of Alzheimer’s in the brain, might contribute to efforts to develop better targeted drugs, or allow us to rethink the drugs we have now. That’s what we hope for.”

The following video, courtesy of Fisher Center for Alzheimer’s Research Foundation, shows some of the brain images captured by iDisco techniques.

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