Plasma P-tau217: Potential biomarker for Alzheimer's?
A new blood test for plasma P-tau217* accurately differentiates Alzheimer's disease (AD) from other neurodegenerative diseases — showing promise as a blood-based biomarker for early detection of AD, according to a study presented at the AAIC 2020 Meeting.
Currently, the brain changes that happen before clinical symptoms of AD manifest can only be reliably detected by PET** scans or cerebrospinal fluid (CSF) tests — methods that are either costly or invasive. Also, these tests may not be readily accessible.
“There is an urgent need for simple, inexpensive, noninvasive and easily available diagnostic tools for Alzheimer’s,” said Dr Maria Carrillo, chief science officer of Alzheimer’s Association. “The possibility of early detection and being able to intervene with a treatment before significant damage to the brain from AD would be game changing for individuals, families, and our healthcare system.”
Among 1,402 participants from three cross-sectional cohorts, plasma P-tau217 accurately predicted AD, with significantly greater accuracy compared with plasma- and MRI-based biomarkers.
“[In addition,] the diagnostic precision of blood P-tau217 was as high as established diagnostic methods, including PET imaging and CSF biomarkers,” the researchers reported.
Furthermore, the researchers found that elevated plasma P-tau217 can be detected up to 20 years prior to the onset of cognitive impairment in individuals with known genetic risk.
“The P-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer’s,” said principal investigator Professor Oskar Hansson from Skåne University Hospital, Malmö, Sweden.
Included in the analysis were three cross-sectional cohorts comprising 1,402 cognitively impaired and unimpaired participants in Arizona (cohort 1), Sweden (cohort 2), and Colombia (cohort 3). [JAMA 2020;doi:10.1001/jama.2020.12134]
In cohort 1, plasma P-tau217 levels discriminated individuals with AD from those without AD (area under the curve [AUC], 0.89) more accurately than other established biomarkers such as plasma P-tau181 and neurofilament light chain (NfL; AUC range, 0.50–0.72; p<0.05).
The second Swedish cohort showed similar findings: plasma P-tau217 distinguished clinical AD dementia from other neurodegenerative diseases with 96 percent accuracy (AUC, 0.96), which was significantly higher than MRI measures, plasma P-tau181, and plasma NfL (AUC range, 0.50–0.81; p<0.001).
This discriminative accuracy also matched the biomarkers measured on CSF and PET scans, such as CSF P-tau181, CSF P-tau217, and tau-PET (AUC range, 0.90–0.99; p>0.15).
In the third Columbian cohort, higher plasma P-tau217 levels were correlated with PSEN1 mutation carriers vs noncarriers as early as the age of 25 — which was 20 years before the estimated age when onset of mild cognitive impairment was expected among mutation carriers.
“While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting,” said Hansson.
“New testing technologies could also support drug development in many ways. For example, by helping identify the right people for clinical trials, and by tracking the impact of therapies being tested,” Carrillo explained.