Plasma p-tau217 disagreed with amyloid PET or CSF in about one in twelve

Design

Retrospective diagnostic accuracy study, single centre

Population

706 research participants (median age 70) with plasma p-tau217 and amyloid PET or CSF

Primary outcome

Discordance of plasma p-tau217 with reference biomarkers

Effect

8.5% discordant; false negative 5.6%, false positive 2.8%

A retrospective Mayo Clinic study of 706 people with a clearly positive or negative plasma p-tau217 result and a reference amyloid PET or CSF test found the blood result was wrong in 8.5%. False negatives (5.6%) were twice as common as false positives (2.8%).

False negatives were independently associated with milder clinical stage, higher BMI and higher eGFR, which fits dilution and faster renal clearance of the marker. False positives were associated with lower eGFR and more advanced dementia. Older age and obstructive sleep apnoea were linked to discordance in general.

The study excluded intermediate results, so real-world discordance will be higher. It is also a research cohort at one centre using one assay. But it gives a practical checklist: a negative p-tau217 in an early, heavier patient with good kidney function deserves less reassurance, and a positive one in someone with chronic kidney disease deserves confirmation before treatment decisions.

• Check eGFR alongside any plasma p-tau217 result before interpreting it.
• Treat a positive p-tau217 in chronic kidney disease as provisional until confirmed by PET or CSF.
• Treat a negative result with caution in early-stage patients with high BMI or high eGFR.
• Consider PET or CSF confirmation before starting an antiamyloid antibody when the blood result is borderline or discordant with the clinical picture.

Why it matters

Blood tests are becoming the gateway to Alzheimer diagnosis, and their errors are not random.

Don't overread it

Intermediate results were excluded, so this underestimates how often blood and reference tests disagree in practice.

The statistics, in plain English

An odds ratio of 1.63 per 10 mL/min for false negatives means each 10-point rise in eGFR raised the odds of a missed positive by about 60%. These are associations within a selected cohort and the numbers of discordant cases are small, hence the wide intervals.

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