REVIEW OF: Ossenkoppele R et al, Nat Aging 2025;5(5):883–896

STUDY TYPE: Multicohort prospective study

Tau-PET can detect Alzheimer’s pathology years before symptoms appear, but it costs up to $6,000 and isn’t widely available. Plasma p-tau217 is a commercially available blood test that costs much less ($200–$400) and reflects the same underlying pathology. This study asked whether the blood test holds up against the gold standard.

Ossenkoppele et al pooled data from nine international cohorts, following 1,474 cognitively normal adults (mean age 69) for nearly four years with both tau-PET and plasma p-tau217 at baseline. The primary outcome was decline on a cognitive composite used in preclinical Alzheimer’s trials; the secondary outcome was progression to mild cognitive impairment (MCI).

The tests performed nearly identically, each accounting for about a third of the variation in cognitive decline and predicting MCI progression at similar rates: roughly 60% higher risk per standard deviation increase across all cohorts. Using both tests together was only marginally better than using either test alone.

CARLAT TAKE
This study was really designed for clinical trialists, not clinicians. Its main finding is that a $200 blood test can predict cognitive decline about as well as a PET scan that costs thousands. The catch: What to do with a positive result? Current guidelines recommend against routine biomarker testing in cognitively normal patients, and disease-modifying therapies in preclinical Alzheimer’s remain unproven—though trials are ongoing. Don’t order the blood test routinely. But if a patient with a strong family history asks what’s available, you can tell them honestly that this test exists, it’s affordable, and the predictive data are now solid. A positive result may not change pharmacologic management yet, but it can inform planning and trial enrollment.