Alzheimer's Blood Test Measures Levels of Phosphorylated Tau
An Indiana University School of Medicine researcher is gaining ground on the development of novel, cutting-edge blood tests to aid in the diagnosis and treatment of Alzheimer’s disease.
Close to 55 million people worldwide, and as many as 6 million people just in the United States, are estimated to have Alzheimer’s disease or related dementias, according to the World Health Organization. With disease modifying therapies becoming available, improving the efficiency of an early diagnosis is critical and blood tests are the best option for affordability and accessibility.
Jeffrey Dage, PhD, senior research professor of neurology and primary investigator at Stark Neurosciences Research Institute, is part of a collaborative study with the Mayo Clinic exploring the utility of blood biomarkers that measure levels of phosphorylated tau (P-tau). In previous studies, Dage has demonstrated that blood levels of P-tau are indicators of the development of Alzheimer’s disease pathology in the brain.
The researchers published their most recent study on P-tau in Nature Medicine. The paper represents the first large community-based exploration into the blood tests. Researchers used more than 1,300 stored blood samples from people between the ages of 30 and 98 in a single county in Minnesota, through the Mayo Clinic Study of Aging.
Dage and Michelle Mielke, PhD, of the Mayo Clinic, have been long-term collaborators, publishing their initial work evaluating tau blood tests in 2016.
The blood biomarkers tested two different measures of phosphorylated tau protein—P-tau181 and P-tau217—which are also found in the brain and are indicators of Alzheimer’s disease pathology. Through these findings, they were able to establish normal reference ranges and evaluate the comorbidity factors that influence protein levels. They also showed that the reference range approach resulted in a test with very high specificity for amyloid and tau PET.
Blood-based biomarkers are the goal in screening for and diagnosing Alzheimer’s disease in the population because they are less costly and invasive than imaging and a lumbar puncture, Dage and Mielke said. However, most work to date has been conducted in memory clinic samples and understanding how these biomarkers can be used in the general population is needed, which is more heterogenous in terms of comorbidities and demographics.
Community-based populations, such as the Mayo Clinic Study of Aging, are critical for establishing the utility of these biomarkers, for screening or diagnosis, and how to interpret them in primary care for the general population, Mielke said. The current work demonstrates that chronic kidney disease, stroke, and myocardial infarction can physiologically contribute to higher blood plasma P-tau levels but not Alzheimer’s disease pathology, Mielke said.
“As a result, individuals with these conditions may test positive, so that it appears they have Alzheimer’s disease when they do not,” Mielke said. “Incorporating this knowledge into the development of cutpoints will enhance accuracy and the future use of the blood-based biomarkers in the population for diagnosis, or even screening purposes.”
Mielke and Dage’s first paper in 2018 evaluating the use of plasma P-tau181 already has more than 130 citations and has initiated a large effort toward the development of improved assays, such as P-tau217 and new research exploring potential uses in many areas of neurodegeneration including the relationship between COVID-19 and neurological symptoms in the elderly.
“This is a very active area of research, and there are now many unique assays to measure phosphorylated tau in blood,” Dage said. “These assays are being compared and used all over the world in research studies and in clinical trials as the research community determines how best to make use these new tools.”
Bruce Lamb, PhD, executive director of Stark Neurosciences Research Institute, said the blood biomarker work is the latest way IU School of Medicine has advanced its Alzheimer’s disease research over the past several years.
“This research includes work being conducted at all stages of development,” Lamb said, “from understanding the basic disease mechanisms to moving novel therapeutics into patients, and everything in between.”
Reference: Mielke MM, Dage JL, Frank RD, et al. Performance of plasma phosphorylated tau 181 and 217 in the community. Nat Med. 2022. doi: 10.1038/s41591-022-01822-2
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