P-Tau217 May Detect Alzheimer Disease, Brain Amyloidosis, Tauopathy

Oskar Hansson, MD, PhD

The results of 2 studies presented virtually at the Alzheimer’s Association International Conference (AAIC) 2020 meeting revealed that blood p-tau217 levels could distinguish Alzheimer disease (AD) from other neurodegenerative disorders as well as other established diagnostic methods, and was also closely linked to build up of amyloid plaques in the brain as measured by positron emission tomography (PET) scan.^1,2

The first study included 3 different cohorts comprising more than 1400 cases and analyzed other current experimental biomarkers such as p-tau181, amyloid beta (AB) 42/40, and neurofilament light chain (NfL) in addition to p-tau217 in both blood and cerebrospinal fluid (CSF) as well as performed PET imaging for tau and amyloid pathology. Patients were pooled from the Swedish-based BioFINDER-2 study, a cohort with neuropathological confirmation of AD from the Arizona Study of Aging and Neurodegenerative Disorders, and from the Colombian autosomal-dominant Alzheimer’s registry, a large cohort with genetically caused AD.

Led by Oskar Hansson, MD, PhD, neurologist, Lund University, the main finding was that blood p-tau217 levels could distinguish AD from other neurodegenerative disorders with diagnostic accuracy between 89% and 98%. Additionally, researchers found that the p-tau217 assessment was more accurate for AD than blood-based tests for p-tau181, NfL, AB42/40, or magnetic resonance imaging (MRI).¹

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“This test, once verified and confirmed, opens the possibility of early diagnosis of Alzheimer’s before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the process,” Hansson said in a statement.

Results from the study also showed that p-tau217 analyzed in blood collected during life could detect tau brain changes measured in brain tissue when analyzed after death. The diagnostic biomarker was able to distinguish those who had plaques and tangles from those without AD pathology, those with plaques and more extensive tangles, and the outcome of tau PET imaging with 89%, 98%, and 93% accuracy, respectively.

“The diagnostic precision of blood p-tau217 was as high as established diagnostic methods, including PET imaging and CSF biomarkers, which are invasive costly and less available,” Hansson and colleagues concluded.

The second study, conducted by Suzanne Schindler, MD, PhD, assistant professor of neurology, Washington University School of Medicine in St. Louis, and colleagues, evaluated the performance of a variety of amyloid and tau measures in blood and found that p-tau217 was more closely linked to a buildup of amyloid plaques in the brain as measured by a PET scan than p-tau181. Results of the study were obtained using mass spectrometry, which mapped the blood plasma tau protein while researchers compared the results to CSF and PET imaging measures.²

Their findings also suggested that measuring levels of several different forms of p-tau in blood over time may enable clinicians and researchers to track the stages of AD progression in people living with the disease. Furthermore, Schindler et al. noted that a blood test for AD that incorporates both amyloid and tau measures may allow for earlier and more accurate dementia diagnoses—not only in research participants, but in clinic patients.

The Study to Evaluate Amyloid in Blood and Imaging Related to Dementia, or SEABIRD (NCT03899844), was launched by the same group of scientists to develop and validate AD blood biomarkers in a cohort that is more diverse and representative of the greater St. Louis region. Diversity in race, socioeconomic status, medical history and cognitive status were all factored into SEABIRD, which expects to enroll more than 1100 individuals.

REFERENCES

1. Janelidze S, Plamqvist S, Quiroz YT, et al. SFRS2-04-03 phospho-tau 181 in plasma and CSF as biomarkers for Alzheimer’s disease. Presented virtually at AAIC 2020. Poster 37520.

2. Bateman RJ, Barthelemy NR, Benzinger TLS, et al. SFRS2-04-01 mass spectrometry measures of plasma AB, tau and p-tau isoforms relationship to amyloid PET, tau PET, and clinical stage of Alzheimer’s disease. Presented virtually at AAIC 2020. Poster 37518.