- Dementia affects around 55 million people worldwide, the majority of whom are diagnosed with Alzheimer’s disease (AD).
- Doctors are able to make a positive diagnosis of AD only when symptoms become severe.
- Earlier diagnosis would allow doctors to begin treatment when people are experiencing mild cognitive impairment (MCI), which could delay the onset of more severe symptoms.
- In a new study, scientists have discovered a biomarker that may help doctors diagnose AD in its earliest stages.
Worldwide, dementia affects at least 55 million people, and the numbers are predicted to rise to 139 million by 2050.
Alzheimer’s disease (AD) is the most common form of dementia and currently affects more than 6.5 million people ages 65 and over in the United States.
But the true numbers are almost certainly higher, as AD is not usually diagnosed until cognitive impairment starts to impact a person’s daily functioning.
According to the Alzheimer’s Association, an additional 5 million people with mild cognitive impairment may be in the earliest stages of AD.
In a recent study, researchers have identified a biomarker that may allow doctors to diagnose AD in people with only mild cognitive impairment (MCI).
Tailored treatment could begin before symptoms become severe by differentiating AD from other forms of dementia at this early stage.
Bin Xu, Ph.D., principal investigator on the study and assistant professor at the Biomanufacturing Research Institute and Technology Enterprise (BRITE) in the Department of Pharmaceutical Sciences at North Carolina Central University, told Medical News Today:
“Low cost, noninvasive tests with high sensitivity and specificity is an urgent unmet need for AD early diagnosis. AD is a slowly progressive disease, which gives us a long window of opportunities to apply medical intervention if we can detect AD changes early.”
The findings were recently published in ACS Chemical Neuroscience.
Biomarkers of Alzheimer’s disease
AD is characterized by the buildup of two proteins in the brain: tau and amyloid beta.
When tau is phosphorylated, it forms neurofibrillary tangles, and amyloid beta accumulates into plaques.
Both plaques and tangles interfere with the transmission of nerve impulses. This is thought to contribute to the symptoms of AD, such as memory loss, cognitive decline, and behavior changes.
Changes in tau proteins, such as phosphorylation, make the proteins more likely to clump together and form the tangles that can prevent nerve impulses from passing between neurons.
Post-mortem research of AD biomarkers
In the new study,the researchers used post-mortem brain tissue from individuals with and without AD to investigate the differences between them.
Using two types of anti-tau antibodies, they identified several p-tau biomarkers in the AD brains that were not found in the non-AD brain tissue.
The researchers identified 3 phosphorylated tau (p-tau) proteins that were biomarkers of AD. The existing biomarkers p-tau 181 and p-tau 217, and a new promising biomarker p-tau 198.
Of the 3 p-tau biomarkers found in the AD brain tissue, two — p-tau 198 and p-tau 217 — were also found in subjects who had shown only mild cognitive impairment (MCI).
How the biomarkers could lead to early AD diagnosis
Diagnosing dementia in the early stages is a key goal of current research.
Early diagnosis of AD allows access to treatment that can help manage symptoms and preserve the person’s functioning level for longer.
Dr. Emer MacSweeney, CEO and consultant neuroradiologist at Re: Cognition Health, told MNT:
“Development of accurate, inexpensive, ubiquitous biomarkers for very early detection of the pathological changes in the brain, consistent with Alzheimer’s disease (AD) pathology, is essential. Access to this type of biomarker, together with new-generation medications to halt or slow progressions of AD at its very early stages, will change the future of the AD pandemic.”
The new biomarker study comes follows a recent proof of concept study that suggested a rapid diagnostic test for AD.
In this latest study, one particular biomarker, p-tau 198, could differentiate between AD brains and non-AD controls and between people with MCI and people with typical levels of cognition.
The researchers suggest that p-tau 198 might be a useful biomarker for detecting MCI, which is often the first stage of AD.
Dr. MacSweeney added that the study’s findings show great potential.
“Their data confirms the utility of previously identified p-tau 181 and p-tau 217 biomarkers, but additionally, their results indicate p-tau 198 is of particular benefit in detecting the presence of abnormal tau protein in the brain, in the very early stages of AD when individuals have no or minimal symptoms,” she said.
“In addition, they conclude p-tau is more effective than the other biomarkers in distinguishing AD pathology from other conditions caused by abnormal tau protein, even at this early stage.”
Large studies on AD biomarkers still needed
Dr. MacSweeney noted some of the study’s limitations, such as its relatively small cohort of post-mortem brains.
“The authors remark on the importance of further larger studies and the requirement for the development of this p-tau 198 biomarker as a potential blood test,” she said.
Indeed, researchers are keen to extend their research to living patients.
“Our discovery came from postmortem brain analysis,” Dr. Xu said.
“We plan to extend to premortem living patients by sampling their blood, cerebral spinal fluid [or both]. This work is in progress.”
Potential to revolutionize early AD diagnoses
According to Dr. Xu, the research team is working on new ways to test biofluids for AD diagnosis.
“The new biomarker p-tau 198 might be identified and quantified by new ultrasensitive technologies, such as [a] single-molecule array, which is about one thousand times more sensitive than a regular ELISA test. We are currently developing such new technologies,” he said.
Dr. MacSweeney added that the findings could “revolutionize” early Alzheimer’s diagnoses.
“This type of work is transformational as current tests for AD, using PET tau and PET amyloid imaging, are very expensive, and measurement of tau in the spinal fluid requires a lumbar puncture[or] spinal tap, which is quite an invasive test,” Dr. MacSweeney explained.
“An easy-to-perform, inexpensive but accurate blood test for p-tau 198 could potentially revolutionize early diagnosis, and hence effective treatment, of AD — especially as we are just seeing the first disease-modifying medications coming on the market.”
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