Researchers have developed a new laboratory test that can measure levels of a “toxic” protein that is highly correlated with developing Alzheimer’s disease (AD) years before any symptoms of cognitive impairment appear. Published on December 5 in Proceedings of the National Academy of Sciences, the findings could be used to identify people at risk for AD, as well as help develop early treatments for the disease, according to researchers.
What clinicians and researchers have wanted is a reliable diagnostic test for Alzheimer’s disease — and not just one that confirms a diagnosis of Alzheimer’s, but a way to detect signs of the disease before cognitive impairment happens, says senior author Valerie Daggett, PhD, a professor of bioengineering in the University of Washington (UW) Molecular Engineering and Sciences Institute in Seattle.
“This disease touches lots of families — it’s just a matter of time until all of us are affected by it in some way,” says Dr. Daggett.
By 2050, the number of U.S. adults over 40 living with dementia is projected to rise from 5.2 million people to 10.5 million, according to an analysis published in January 2022 The Lancet. The study predicts that the number of people with dementia will go up in every country in the world, resulting in a near tripling in the global rate of dementia.
New Test Could Determine Who Needs Treatment and Who Can Have ‘Peace of Mind’
Most people receive a diagnosis of Alzheimer’s only after they develop signs of the disease, such as memory loss. But changes in the brain related to AD begin years before these signs appear — this is called preclinical Alzheimer’s disease, according the Alzheimer’s Association.
These findings suggest that this test can diagnose Alzheimer’s and accurately predict the transition from preclinical to clinical disease, says Martin Sadowski, MD, PhD, professor of neurology and psychiatry at the NYU Grossman School of Medicine and a neurologist who specializes in dementia and Alzheimer’s at NYU Langone Health, both in New York City. Dr. Sadowski was not involved in this research. “Hence it can tell apart who is at imminent risk of cognitive decline and who can have peace of mind,” he says.
The new test could provide an accessible way for people to find out if they have AD — and if they do have evidence of the toxic protein, they can begin taking any available treatments to slow down progression, as well as make important lifestyle modifications, says Daggett.
Sadowski agrees, saying, “People identified as at risk can be offered therapeutics delaying disease onset, [such as] lecanemab.”
Although There Isn’t a Cure for AD, Potential Therapies and Lifestyle Changes May Improve Outcomes
Currently, there’s only one approved disease-modifying treatments for AD: aducanumab (Aduhelm). If Alzheimer’s could be detected earlier, that could pave the way for more treatments that could help slow down AD before irreparable damage occurs, according to the authors.
Although not yet approved by the U.S. Food and Drug Administration (FDA) to treat early AD, lecanemab is monoclonal antibody that appears to reduce markers of amyloid in early Alzheimer’s and resulted in moderately less decline on measures of cognition and function at 18 months compared with a placebo. The findings were published on November 29, 2022, in The New England Journal of Medicine.
There’s also evidence that lifestyle modifications can make a big difference in dementia — a study published in February 2022 in The Lancet found that 12 modifiable risk factors, including hypertension, smoking, obesity, alcohol, physical activity, and diabetes, could account for 40 percent of dementia cases worldwide.
Test Can Accurately Predict Who Currents Has AD and Who May Develop It Later
According to researchers, the early “seeds” in the brain that later “grow” into Alzheimer’s disease are called amyloid beta proteins. Instead of behaving like healthy proteins in the brain, these amyloid beta proteins misfold and clump together, forming small masses called oligomers.
For reasons that are still not completely understood by scientists, the oligomers are thought to cause the damage that eventually results in Alzheimer’s.
Researchers found that SOBA (soluble oligomer binding assay) — could detect oligomers in the blood of patients with Alzheimer’s disease. In the control group, which only included people who showed no signs of cognitive impairment at the time their blood samples were taken, 11 people were found to have oligomers.
Ten of those people were able to be medically followed, and all were eventually diagnosed with mild cognitive impairment (MCI) or brain pathology consistent with Alzheimer’s. The test had identified the at-risk individuals before the presence of any symptoms, and the blood samples from people who never went on to develop cognitive impairment lacked the toxic oligomers.
Mild cognitive impairment is an early stage of memory or cognitive ability loss. People with MCI are at a significantly increased risk of developing dementia, but some people with MCI remain stable for many years, per Mayo Clinic.
Test Results Were Confirmed Via Autopsy
SOBA uses a special synthetic test surface that’s able to bind with proteins in the blood, thereby allowing it to be tested for the presence of the toxic oligomers.
In another evaluation of the test, investigators used the test on blood samples from 310 research subjects who had previously made their blood samples and some of their medical records available for Alzheimer’s research. At the time the blood samples had been taken, the participants showed no signs of cognitive impairment, mild cognitive impairment, Alzheimer’s disease, or another form of dementia.
SOBA detected oligomers in the blood of individuals with mild cognitive impairment and moderate to severe Alzheimer’s. Researchers were able to examine the brains via autopsy in 53 cases after a participant died, and in 52 of those cases, the blood samples which had been taken years before their deaths contained toxic oligomers.
“It appears to accurately predict risk of cognitive decline in cognitively normal individuals and accurately separates Alzheimer from other neurodegenerative diseases,” says Sadowski.
Researchers Hope to Make Test Widely Affordable and Widely Available
Daggett’s team is working with scientists at AltPep, a UW spinout company, to develop SOBA into a diagnostic test for oligomers.
“We want something that can give us a readout of what’s going on in the brain without having to do a lumbar puncture or expensive imaging, which is what’s done now (to diagnose AD) in the best of cases,” says Daggett.
SOBA requires a general simple blood test that could inexpensively available at most labs — even in a doctor’s office — as opposed to requiring very fancy technology and processing, she says. The costs for those procedures can be between $5,000 and $8,000 dollars, she adds.
“Also, SOBA appears to be much more sensitive and specific — so much more accurate than the other testing methods,” says Daggett.
These newly published findings are just the start, she says. “We’ve also evaluated samples from two other cohorts and are getting other samples and will continue to do so — that’s needed to validate what we’re finding,” says Daggett.
Sadowski agrees that the sample of preclinical patients in this study is relatively low. The test should be validated on a larger group of preclinical patients who need to be thoroughly characterized using Alzheimer’s imaging biomarkers like positron emission tomography (PET) scans, he says.
SOBA Could Be Used to Identify Other Diseases, Such as Parkinson’s Disease and Type 2 Diabetes
“The FDA has approved our breakthrough status application to develop this test,” says Daggett.
Researchers believe the test has further potential — in principle, this same technology can be used to detect other amyloid diseases. “Not just Alzheimer’s, but also Parkinson’s disease, type 2 diabetes, and more. The hope is that this method can help in diagnosing and studying many other ‘protein misfolding’ diseases,” says Daggett.
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