The accumulation of disordered, phosphorylated tau proteins in the brain is a defining neuropathological feature of Alzheimer’s disease (AD). Currently, tests to assess tau in the clinic are limited to PET scans or cerebrospinal fluid (CSF) analyses, which involve invasive and costly lumbar punctures. To meet the need for minimally-invasive and rapid tests for tau in people with suspected AD, several groups have developed plasma assays for blood-based biomarkers, including phosphorylated forms of the tau protein such as p-tau181 and p-tau217.
In their research study, published in the Journal of the American Medical Association on 28 July, Dr Sebastian Palmqvist and colleagues set out to establish whether a blood plasma test for p-tau217 could accurately differentiate AD from other neurodegenerative disorders. They also sought to compare the p-tau217 test to plasma, CSF and brain imaging tests for other AD-associated proteins such as p-tau181, neurofilament light chain (NfL) and beta-amyloid. To do this, they assessed biosamples and scans from participants in three separate cohorts: an Arizona-based Neuropathology Cohort, the Swedish BioFINDER-2 Study, and the Colombian Autosomal Dominant AD Registry.
In total, 1402 participants were included in the researchers’ analyses, which showed that a plasma p-tau217 test could accurately distinguish people with clinically diagnosed AD dementia from those with other neurodegenerative disorders. In addition, levels of plasma p-tau217 were strongly correlated to the amount of tangled tau detected on PET scans of the brain, and were elevated early in the AD disease process. In comparison to plasma p-tau181, plasma NfL and MRI imaging, plasma p-tau217 had a higher clinical diagnostic accuracy, and performed similarly well to CSF measures of AD pathology. Together, these results add to a substantial body of work in clinical study participants confirming the utility of minimally-invasive blood tests for tau as a diagnostic or monitoring tool for AD. Further studies are now required in larger, unselected – and more ethnically diverse – primary care populations.
