More than 6 million Americans are living with Alzheimer’s disease, and by 2050, that number is projected to reach 12.7 million, according to the Alzheimer’s Association. There is currently no cure for the disease, but researchers have been working to create therapies that can slow or stop its progression. A research team at Washington University School of Medicine identified a new potential target for treatment that could delay or reverse damage to the brain caused by Alzheimer’s.
Currently, most treatments for Alzheimer’s target beta proteins that aggregate in the brain and create buildup known as amyloid plaques, which are linked to the memory and cognition symptoms of Alzheimer’s. “Other treatments being studied focus on another protein called tau,” notes principal investigator Dr. Carlos Cruchaga, the Barbara Burton and Reuben M. Morriss III Professor of Psychiatry. “However, Alzheimer’s is a complex disease. We need more options for treatment, so we have to move beyond looking at just beta and tau.”
There are several other proteins in the brain that can contribute to the creation of plaques. Cruchaga and his team have been looking to find those whose function in the brain and other tissues are altered by the progression of the disease. “We know the pathway to Alzheimer’s begins 20 to 25 years before clinical onset, or the appearance of symptoms,” he explains. “In this study, we were able to identify proteins associated with the risk of developing the disease, using a combination of proteomics (the study of proteins), genetics and data science.”
The researchers analyzed protein levels from brain tissue, cerebrospinal fluid and blood plasma samples gathered from more than 1,500 people. Half of the samples came from patients with a clinical diagnosis of Alzheimer’s and the other half came from people who are considered cognitively normal. Using statistical and machine learning techniques, they were able to connect 274 proteins to the disease and identify some that contribute to the damage that can lead to Alzheimer’s. “To treat Alzheimer’s, we need approaches that can address multiple stages of the disease,” Cruchaga notes. “Targeting these proteins could help with both its onset and progression.”
Along with identifying the proteins, the team also found existing drugs that have therapeutic potential against them. The 15 treatments identified already have approval by the Food and Drug Administration for other purposes. This means that clinical trials for treatment of Alzheimer’s could potentially begin sooner. “The safety analysis has already been done,” Cruchaga says. “The next step for our research is to confirm we can delay or stop the progress of the disease in mouse models and then go to clinical trials, so we are moving in that direction.” The study also identified treatments that could be used to target faulty proteins linked to Parkinson’s disease, stroke and amyotrophic lateral sclerosis.
The study was funded by the National Institute on Aging of the National Institutes of Health and is published in the journal Nature Neuroscience. “We are quite happy with the results,” Cruchaga says. “I think we’re just seeing the tip of the iceberg when it comes to identifying potential targets for treatment. These and other approaches are going to make a big difference. We may not have found a cure, but we now have the tools to really help patients.”
alzheimer’s by the numbers
- One in nine people age 65 and older has Alzheimer’s.
- Almost two-thirds of Americans with Alzheimer’s are women.
- Among 70 year-olds, 61% of those with Alzheimer’s are expected to die before the age of 80 compared with 30% of people without the disease.
- Between 2000 and 2019, deaths from Alzheimer’s have increased 145%.
- In 2021, Alzheimer’s and other dementias will cost the U.S. $355 billion.
Source: Alzheimer’s Association