Researchers are honing in on the best blood biomarker to detect Alzheimer disease (AD) at its earliest stages and plasma tau phosphorylated at threonine 217 (P-tau217) is a front runner. According to a new study in JAMA Neurology, blood levels of P-tau217 are increased in early preclinical AD, and the change happens before tau pathology is detected on positron emission tomography (tau-PET). Dr. Shorena Janelidze of Lund University and colleagues compared changes in blood P-tau217 levels in preclinical and prodromal AD relative to changes in cerebrospinal fluid (CSF) P-tau217 and PET measures in 314 cognitively normal older adults and 176 with mild cognitive impairment (MCI) participating in the Swedish BioFINDER-2 study. Blood levels of P-tau217 were elevated in amyloid-positive, cognitively unimpaired older adults before tau aggregates became detectable by tau-PET, the researchers report. In cognitively normal adults and in those with MCI, event-based modeling approaches predicted that increases in both plasma and CSF P-tau217 would precede changes in tau-PET in the entorhinal cortex, an early region of neurofibrillary tangle formation, followed by more widespread brain tau-PET changes. Thirty-six of 38 cognitively normal adults in whom plasma and PET measures of tau were discordant showed positive plasma P-tau217 and negative tau-PET in the entorhinal cortex, they note. The authors of a linked editorial say it's also noteworthy that individuals with negative baseline tau-PET but positive plasma P-tau217 showed "accelerated longitudinal increases in the entorhinal cortex tau-PET signal, suggesting that baseline plasma measures were picking up biologically meaningful tau pathology that was below the threshold of PET detection." In an earlier study, the same research team showed that plasma P-tau217 accurately differentiated patients with AD from controls and patients with other non-AD neurodegenerative conditions (https://bit.ly/3kj8U8Q). Taken together, the data "support plasma P-tau217 as a biomarker of tau pathology at the earliest stages of AD," Dr. Elisabeth Thijssen and Dr. Gil Rabinovici of the Memory and Aging Center, University of California, San Francisco, write in their editorial. They note that progress in developing blood-based biomarkers for AD has generated "justifiable excitement in the field" and there are many reasons to be "optimistic that reliable and scalable blood tests for AD are truly on the horizon. The standardization and reproducibility of plasma assays will be accelerated by lessons learned from the development of CSF biomarkers and by international AD fluid biomarker consortia focused on this mission." "It seems like only a matter of time before a panel of blood tests will be widely available" to assess amyloid, tau and neurodegeneration brain changes in research and in the clinic, transforming the diagnosis and care of patients in the earliest stages of AD," the editorial writers conclude. The study had no commercial funding. —Reuters Staff Source
