Imaging technology allows 3-D visualization of Alzheimer’s-related plaques

The Fisher Center for Alzheimer's Research Foundation is funding a new technology that allows greater visualization of amyloid plaques as well as other Alzheimer’s markers, such as tau proteins and vasculature and microglia activation.

3-D rendering of three amyloid plaques (PRNewsFoto/Fisher Center for Alzheimer's)

3-D rendering of three amyloid plaques

A nonprofit dedicated to finding a cure for Alzheimer’s disease is funding a new technology that allows greater visualization of amyloid plaques as well as other Alzheimer’s markers, such as tau proteins and vasculature and microglia activation.

The technology was created by scientists at the New York City-based Fisher Center for Alzheimer’s Research Foundation and described in a study published in the scientific journal Cell Reports. Dr. Marc Flajolet, lead author of the study and team leader, said the new technology platform allows the visualization of those markers in larger, three-dimensional amyloid patterns (TAPs) in greater volume. Fisher Center scientists conducted their research on brain tissue from mice and frozen human brain samples of deceased Alzheimer’s patients.

“We are proud that the funding we provide has resulted in innovative, never- before-seen imaging of what causes Alzheimer’s disease,” said Kent Karosen, Fisher Center president and CEO. “The Fisher Center scientists are working diligently to better understand the cause and cure of the disease and with the ability to visualize the causes of Alzheimer’s, we’re one step closer to a cure.”

Flajolet said the Fisher’s team employed the “iDISCO” visualization method involving targeted molecular labeling, tissue clearing and light-sheet microscopy.
The new technology allows 3-D visualization in five different brain regions, better mapping and automated detection enabling faster quantification of plaques, which Flajolet characterized as a cheaper alternative to standard beta amyloid plaque labeling.

“Now we can look at much bigger volumes and see bigger structures that we could not see before in higher resolution,” he explained. “Before this, there were more limitations. We were unable to get the detail we get now.”

He said the technology may open doors of possibility for further Alzheimer’s research that might lead to new Alzheimer’s disease classifications.

“What we have discovered is that amyloid plaques (the groupings of protein that mark the presence of Alzheimer’s) organize themselves into strange patterns that are distributed in different ways, in some cases layers of plaques,” he said. “We don’t yet understand the meaning. But if we could organize patients by how those plaques presented themselves in the brain through retrospective studies and learn the symptoms those patients expressed, we might find ways to categorize stages of the disease differently.”

He said that today, new drugs are tested on Alzheimer’s patients without regard to the level or patterns of plaque in their brains.

“But perhaps, like depression or schizophrenia, not all patients respond to the same drugs. Could it be the same for Alzheimer’s?” Flajolet wondered. “If we are dealing with brains and we know patient symptoms, there is a chance we could propose some categories so the next clinical trial might be used on different patients expressing different patterns. It might only work on 10 percent of patients, but it could open doors.”

The Fisher Center for Alzheimer’s Research Foundation was established in 1995 by philanthropists Zachary Fisher and David Rockefeller. Paul Greengard, who leads the research center, is a Nobel Prize-winning scientist, leads a team of 50 researchers seeking a cure for Alzheimer’s.

Here’s a video from the Fisher Center demonstrating the visualization:

Photo: Fisher Center for Alzheimer’s Research Foundation

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