By the time memory loss and cognitive decline appear in people with Alzheimer’s disease, their brains already are significantly damaged, dotted with clumps of a destructive protein known as amyloid beta.
For years, scientists have sought methods to help identify brain changes associated with Alzheimer’s earlier in the disease process.
Doing so they can stop or even reverse the changes before they severely affect people’s lives.
Now, researchers at Washington University in St. Louis have developed a chemical compound, Fluselenamyl.
The compound, described in a paper in Scientific Reports, potentially could be used in brain scans to identify the signs of early-stage Alzheimer’s disease or to monitor response to treatment.
Amyloid plaques are one of the most telltale findings in the brains of people with Alzheimer’s disease.
The neurons near such plaques are often dead or damaged, and this loss of brain cells is thought to account for difficulty with thinking, memory loss and confusion experienced by Alzheimer’s patients.
Amyloid plaques can be either diffuse or compact.
The compact kind has long been associated with the disease, but they can also be found in the brains of elderly people without Alzheimer’s disease.
The researchers believe that diffuse plaques may mark the earliest stages of the disease.
Using human amyloid beta proteins, the researchers showed that Fluselenamyl bound to such proteins 2 to 10 times better than each of the three FDA-approved imaging agents for detecting amyloid beta.
In other words, Fluselenamyl detected much smaller clumps of the protein, indicating that it may be able to detect the brain changes associated with Alzheimer’s disease earlier.
An experiment comparing mice genetically predisposed to develop amyloid plaques with normal control mice showed the high sensitivity for amyloid beta and low binding to healthy white matter.
Furthermore, the researchers showed that when Fluselenamyl with the radioactive atom is injected intravenously into mice, the compound could cross the blood-brain barrier, bind to any plaques in their brains and be detected by PET scan.
In mice without plaques, the compound is quickly flushed from the brain and then excreted from the body.
The next step is to move to testing in patients.
The researchers already have submitted an application to the National Institutes of Health (NIH) for a phase 0 trial, to establish whether Fluselenamyl is safe for use in humans and behaves in the human body the same way it behaves in mice.
Phase 0 trials involve a low dose given to a small number of people to learn how a molecule is processed in the body and how it affects the body.
News source: Washington University in St. Louis
Figure legend: This Knowridge.com image is credited to Ping Yan and Jin-Moo Lee.