Lilly's Novel P-tau217 Blood Test Demonstrates High Diagnostic Accuracy for Alzheimer’s Disease in Landmark JAMA Publication

Source | Jike Pharma News

On July 28, the results of a large international study on Eli Lilly and Company’s new blood test for diagnosing Alzheimer’s disease (AD) using P-tau217 were published in the Journal of the American Medical Association (JAMA). The results showed that P-tau217 (tau protein phosphorylated at threonine 217) significantly outperformed other blood-based biomarkers or magnetic resonance imaging (MRI) in distinguishing AD from other neurodegenerative diseases. P-tau217 demonstrated promising applications in diagnosing AD and enabling early diagnosis in individuals with known genetic risks; for populations carrying susceptibility gene mutations, it is expected to detect AD up to 20 years before the anticipated onset date, such as prior to the emergence of early cognitive impairment.

For many years, the diagnosis of Alzheimer’s disease has been based on the characteristic presence of amyloid plaques and tau tangles in the brain, which were typically identified only after the patient’s death. Over the past two years, significant advances have been made in the development of blood tests for amyloid proteins. According to this new study, measuring P-tau217, a form of tau protein found in tangles, can provide a relatively sensitive and accurate indicator for detecting plaques and tangles, holding promise for the antemortem diagnosis of Alzheimer’s disease.

This cross-sectional study comprised three cohorts, including patients from the Arizona Neurodegenerative Disease Program neuropathology cohort, the Swedish BioFINDER-2 cohort, and the Colombian autosomal dominant Alzheimer’s disease (AD) kindred cohort. The results demonstrated that P-tau217 accurately distinguished AD from other neurodegenerative diseases in both the Arizona-based neuropathology cohort and the Swedish BioFINDER-2 study. In the third, Colombian cohort, blood P-tau217 levels were elevated in mutation carriers 20 years before the expected symptom onset and were associated with memory performance.

Researchers evaluated this novel P-tau217 blood assay in 1,402 study participants with and without cognitive impairment from well-established cohorts in Arizona, Sweden, and Colombia. Coordinated by Lund University in Sweden, the study included 81 participants from Arizona enrolled in the Banner Sun Health Research Institute Brain Donation Program, who underwent clinical assessments and provided blood samples during the final years of their lives, followed by neuropathological evaluation after death; 699 participants from the Swedish BioFINDER study, who underwent clinical, brain imaging, cerebrospinal fluid (CSF), and blood-based biomarker assessments; and 522 carriers and non-carriers of pathogenic mutations associated with autosomal dominant Alzheimer’s disease (ADAD) from the world’s largest ADAD cohort in Colombia.

In the Banner Sun Health Research Institute brain donation cohort in Arizona, plasma P-tau217 assays distinguished brain donors with subsequent neuropathological diagnoses of “intermediate or high likelihood Alzheimer’s disease” (i.e., characterized by plaques and tangles that had spread at least to the temporal lobe memory regions or beyond) with an accuracy of 89%; differentiated individuals with versus without a diagnosis of “high likelihood Alzheimer’s disease” with an accuracy of 98%; and higher P-tau217 levels correlated with higher brain tangle counts only among those who also had amyloid plaques.

In the Swedish BioFINDER study, this assay distinguished patients with a clinical diagnosis of Alzheimer’s disease from those with other neurodegenerative diseases with 96% accuracy, comparable to tau PET imaging and CSF biomarkers, and superior to several other blood-based assays and MRI measures; it also differentiated patients with and without abnormal tau PET scans with 93% accuracy.

In the Colombian cohort, this assay was able to distinguish mutation carriers from non-carriers 20 years before their estimated age of onset for mild cognitive impairment.

In each analysis, P-tau217 outperformed P-tau181 (another epitope of tau tangles and a potential biomarker for blood-based diagnosis of AD) and other investigational blood tests.

Dr. Oskar Hansson, Professor of Clinical Memory Research at Lund University in Sweden and leader of the Swedish BioFINDER study, stated, “The P-tau217 blood test holds great promise for the diagnosis, early detection, and research of Alzheimer’s disease. Although further work is needed to optimize the assay and conduct broader validation before clinical implementation, blood testing may prove particularly useful in improving the identification, diagnosis, and care of individuals in primary care settings.”

Dr. Jeffrey Dage, Senior Research Advisor at Eli Lilly and Company, stated, “Differentiating AD pathology from other types of cognitive impairment is a critical step in understanding how AD affects patients. As research advances, we are able to identify AD earlier, and we hope to conduct further studies in appropriate populations in the future. From diagnostic tools to therapeutic opportunities, Lilly and Avid remain committed to advancing robust research in AD.”

Eli Lilly and Company and its wholly-owned subsidiary, Avid Radiopharmaceuticals, which is dedicated to the discovery and development of radiopharmaceuticals and imaging methods, are conducting research on P-tau217 as a pathological biomarker for Alzheimer’s disease (AD). Eli Lilly will continue to optimize the assay and determine its potential role in clinical practice. Additional research data on P-tau217 will be presented at upcoming scientific conferences, including the Alzheimer’s Association International Conference (AAIC) (July 27–31) and the Clinical Trials on Alzheimer’s Disease (CTAD) Conference (November 4–7).

References:

[1] New blood test shows great promise in the diagnosis of Alzheimer's disease. Retrived 2020-7-28 from https://www.eurekalert.org/pub_releases/2020-07/lu-nbt072820.php

[2] Lilly's P-tau217 Blood Test Shows High Accuracy in Diagnosis of Alzheimer's Disease in Data Published in JAMA. Retrived 2020-7-28 from https://investor.lilly.com/news-releases/news-release-details/lillys-p-tau217-blood-test-shows-high-accuracy-diagnosis

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