Blood p-tau217 Test Matches Cerebrospinal Fluid Test in Accuracy for Identifying Alzheimer's Pathology

A blood test that identifies amyloid-β plaques and tau tangles, the core pathology of Alzheimer's disease, showed accuracy on par with the existing cerebrospinal fluid (CSF) test. The result was published in Nature Medicine by a joint research team from Washington University School of Medicine in the United States and Lund University in Sweden.

1,759 People in Two Cohorts, Compared Against PET Imaging

The researchers used mass spectrometry to measure the ratio of phosphorylated tau217 to nonphosphorylated tau (%p-tau217) in plasma from 1,422 people in the Swedish BioFINDER-2 cohort and 337 people in the U.S. Knight ADRC cohort. Cerebrospinal fluid from the same people was measured with an FDA-cleared automated immunoassay used in clinical practice, and the presence of actual brain pathology was determined using positron emission tomography (PET) as the reference. For identifying amyloid PET status, the area under the curve (AUC) of both tests was 0.95 to 0.97, and for tau PET status the blood test was generally better, at 0.95 to 0.98.

Looking only at patients with mild cognitive impairment or mild dementia, who are the target for antibody treatments, accuracy, positive predictive value and negative predictive value were 89% to 90% for amyloid and 87% to 88% for tau. Using two cutoffs and sending only the intermediate zone for additional testing raised this to 95%.

Significance and Limits

Because it widens the ways to confirm pathology without a lumbar puncture or expensive PET, it could improve access to diagnosis. However, the participants came mainly from specialized research cohorts, and mass spectrometry-based testing is hard to roll out immediately at general medical institutions. Further validation is needed across diverse racial groups and in primary care settings.