The discovery of a new biomarker may help physicians diagnose Alzheimer's disease earlier, and with a simple blood test, once a person develops mild cognitive impairment. Photo by pasja1000/Pixabay
Nov. 9 (UPI) -- U.S. scientists have discovered a new tool that may help physicians diagnose Alzheimer's disease earlier -- and with a simple blood test -- once a person develops mild cognitive impairment and before significant neurological damage occurs.
The study's findings were published Wednesday in the journal ACS Chemical Neuroscience.
The progressive illness, which begins with mild memory loss, may lead to inability to carry on conversations and respond to elements in their environment.
"One practical application we can envision is [a] blood-based diagnostic test for checking early signs of Alzheimer's disease," Bin Xu, the study's principal investigator at North Carolina Central University's Biomanufacturing Research Institute & Technology Enterprise, known as BRITE, told UPI in an email.
Xu also is assistant professor in the Department of Pharmaceutical Sciences and faculty co-director of the Neurobehavioral Core Facility at North Carolina Central University.
A definitive diagnosis of Alzheimer's disease -- the most common form of dementia, affecting roughly 6 million Americans ages 65 and older and rising as the population ages -- was once only possible after a person's death.
Recent studies of biological markers -- or "biomarkers" -- used to predict, diagnose and monitor specific diseases in the body have led to the development of brain scan and spinal fluid tests for Alzheimer's disease in people still living.
But these tests focus on helping to diagnose severe, advanced Alzheimer's disease, distinguishing it from related neurodegenerative disorders.
Xu said the research team from BRITE and Duke University Medical Center's Department of Neurology discovered a new biomarker in the brains of deceased patients with Alzheimer's disease that may allow earlier detection.
Now, they are extending their work to testing blood and cerebral spinal fluid from living patients.
"We are also developing ultra-sensitive detection technologies for such application," Xu said. "It is possible that we translate our discoveries from [the lab] to bedside applications in several years."
An outside expert, Dr. Glen R. Finney, described the research as a well-designed study "building on decades of research" and "moving our understanding forward" of the early pathology of Alzheimer's disease and how it differs from other types of dementia.
Worldwide, an estimated 50 million people are living with dementia, and 60% to 70% of the cases are caused by Alzheimer's disease, Xu said.
So, Xu said, there is "an urgent unmet need" for creating tests "with high sensitivity and specificity" for early Alzheimer's diagnosis.
Alzheimer's "is a slowly progressive disease, which gives us a long window of opportunities to apply medical intervention if we can detect [Alzheimer's-related] changes early," Xu said.
"Currently, there are no well-established, minimally invasive tests available for early AD diagnosis. Our test, once validated in blood, will have the advantages of low cost and minimal invasiveness."
In the study, the North Carolina-based researchers examined subtle changes in a brain protein called tau that can make it more likely to clump -- a hallmark of Alzheimer's disease that causes neuron loss and impaired memory.
Using post-mortem brain tissue from patients with Alzheimer's disease and healthy controls, the researchers searched for additional p-tau biomarkers to help diagnose Alzheimer's disease, possibly in its earlier stages.
Previous research has identified tau tangles or "phosphorylation" of tau, at two specific sites, called p-tau181 and p-tau217, used to diagnose advanced Alzheimer's disease.
In 2020, the Food and Drug Administration approved flortaucipir, or AV-1451 -- the first tau biomarker approved as a diagnostic tool for Alzheimer's disease -- to be used with positron emission tomography, or PET, scans to diagnose late-stage illness.
Other FDA-approved diagnostic tests, introduced over the past decade, help detect beta-amyloid plaques in the brains of living patients.
The North Carolina scientists discovered a third site-specific tau tangle, p-tau198, that could distinguish Alzheimer's disease from other neurodegenerative diseases involving tau tangles -- and also could differentiate the brain tissue of patients with mild cognitive impairment, an early sign of Alzheimer's disease, from those without it.
"Both p-tau217, discovered by other research groups and is currently under development by Eli Lilly, and the new biomarker p-tau198 we discovered, showed promising results for early disease detection in our studies," Xu said.
Finney, the outside expert who is a professor of neurology at Geisinger Commonwealth School of Medicine and director of the Geisinger Health Memory and Cognition Program, told UPI that this study "increases our knowledge of the molecular and location features of proteins involved in Alzheimer's disease and other dementias, which someday may help us to identify what types of problems may be developing in the brain before they do as much damage."
Finney added: "If this antibody probe or others like it can be used to mark better where the earliest changes in the brain are occurring in people and tell the difference between early changes of Alzheimer's disease versus other early changes of dementia and those not developing dementia, that helps to find future treatments for Alzheimer's disease."
However, since this study examined brain tissue from deceased individuals, it "needs to be developed further to see if it similar detection of markers like this one can be done successfully in people during their life," said Finney, who is on the board of the Greater Pennsylvania Chapter of the Alzheimer's Association.
"A lot of research has been done in general for developing both brain imaging, spinal fluid, and blood tests for proteins like this but I believe this is a newer way of looking as phosphorylated tau, one of the main proteins in Alzheimer's disease," he added.
Xu said the team of BRITE/Duke researchers have additional new biomarkers being developed.
"We believe our discovery approach may work for finding new protein biomarkers in other aging-related neurodegenerative diseases, such as Parkinson's disease and Lou Gehrig's disease," Xu said.