At the Alzheimer’s Association International Conference (AAIC) 2020, results from several studies reported potential blood test measures for diagnosis and disease monitoring of Alzheimer disease (AD). Most relied on assaying for the presence of various isoforms of phosphorylated tau, p-tau217 and p-tau181.
Of the studies, results from 2 were also published in the Journal of Experimental Medicine and JAMA. The 2 studies used differerent methods to assay blood levels of tau species, mass spectrometry and immunoassay, and both found significant correlations with amyloid-b levels on positron emission tomography (PET) and in cerebrospinal fluid.
With a typical blood sample, the mass spectrometry level of p-tau217 and amyloid levels on PET had a .93 correspondence (ROC area under the curve); with a larger blood sample (20mL) this increased to .99). Data from a third study, the SEABIRD study (NCT03899844) presented at the meeting showed that serum levels of p-tau181 and p-tau217 were 91% and 96% sensitive for a positive finding on a tau PET scan.
“There is an urgent need for simple, inexpensive, noninvasive and easily available diagnostic tools for AD. 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,” said Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer. “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.”
The large sample sizes in these studies (from 500 to 1,000) and similar findings with varied methods provide strong evidence that a phospho-tau blood test, perhaps as part of a panel of biomarkers, is feasible. Although further studies are needed along with clinical trials and validation for clinical use may take a few years, this could allow development of a more clinically useful objective diagnostic test for AD. In addition, further validation of this test will be of great use in clinical trials evaluating potential treatments for AD because it will add yet another refined measure to define participant populations and control potential cofounders in such trials.
Jason A. Ellis, MD; Benjamin W. Y. Lo, MD; Chirag G. Bhatia, BS; Yona Feit; Steven Mandel, MD; and Dana Shani, MD
Jakai D. Nolan, DO, MPH, and Jacqueline A. Nicholas, MD, MPH
Monideep Dutt, MD; Jamika Hallman-Cooper, MD; Ekta Bery, MD; Mohammed Shahnawaz, MD; and Grace Gombolay, MD