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Do treatments that reduce beta-amyloid in the brain help improve cognitive health by normalizing brain cell activity?
Stephanie Buss, M.D.
Beth Israel Deaconess Medical Center
Boston, MA - United States
Background
Beta-amyloid is a sticky protein fragment that forms abnormal clumps called plaques in the brain, a key hallmark of Alzheimer’s. Researchers have developed antibody therapies that use the body’s own immune system to target and remove beta-amyloid plaques. Lecanemab is an amyloid immunotherapy (antibody) that has shown beta-amyloid-clearing abilities in clinical trials and has been approved by the FDA. Scientists, however, remain uncertain exactly how lecanemab and other amyloid-removing therapies may affect cognition (brain function). To date, lecanemab has shown either modest or inconsistent effects on slowing cognitive decline.
In preliminary studies, Dr. Stephanie Samantha Buss and colleagues have been examining nerve cells in the brain that become overly excited (or overstimulated) in people with Alzheimer's or mild cognitive impairment (MCI, a condition of subtle memory loss that may precede Alzheimer’s). They found that when nerve cells in certain parts of the brain become overstimulated, nerve cell communication across brain networks becomes inhibited and leads to cognitive loss. The researchers also point to studies indicating that changes in nerve cell communication may be linked to levels of beta-amyloid in the brain. Such findings indicate the need to study how removing beta-amyloid, through treatments such as lecanemab, may improve cognitive health by impacting nerve cell “excitability” and communication.
Research Plan
Dr. Buss and team will now devote their research grant to conducting such a study. For this effort, they will recruit and test two groups of older participants with early Alzheimer’s or MCI: 33 who undergo lecanemab treatment over 18 months and 30 who do not receive treatment. Using sophisticated techniques that measure electrical activity in the brains of their participants, they will assess nerve cell excitability in specific regions linked to early Alzheimer’s, as well as brain cell communication across brain networks. These results will then be analyzed to determine whether lowering beta-amyloid levels in the brain reduce local nerve cell excitability and promote network-level communication. The researchers will also determine if this therapy can reduce cognitive decline in participants receiving lecanemab over 18 months, compared with those who do not receive treatment.
Impact
Results from Dr. Buss’s study could shed new light on the role of beta-amyloid in brain cell function. It could also lead to improved amyloid-reducing treatments that more effectively preserve cognitive function in Alzheimer’s.
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