Plasma pTau217 closely matched cortical tau in an autopsy series

Design

Retrospective antemortem plasma and postmortem tissue validation study

Population

32 people with dementia from one academic memory clinic (19 Alzheimer disease, 13 frontotemporal lobar degeneration)

Primary outcome

Correlation of plasma and temporal cortex pTau217

Effect

Partial rho 0.73 to 0.78; AUC 0.88 to 0.94 for Alzheimer vs non-Alzheimer

This study from the Leuven memory clinic linked plasma taken in life with brain tissue at autopsy in 32 people with dementia: 19 with Alzheimer disease and 13 with frontotemporal lobar degeneration.

Plasma pTau217, measured on the Lumipulse G platform, correlated strongly with pTau217 in the inferior temporal cortex (partial rho 0.73 to 0.78). The N-terminal plasma assay and the pTau217 to amyloid-beta 1-42 ratio fitted cortical levels slightly better than the mid-region assay. All plasma markers separated Alzheimer disease from frontotemporal lobar degeneration with an area under the curve of 0.88 to 0.94. After adjustment for each other, plasma pTau217 tracked tau tangle density rather than amyloid plaque density.

The point for clinicians ordering the test is that a raised plasma pTau217 reflects tau pathology in the cortex, not only amyloid. The series is small and confined to people who already had dementia.

• Read a raised plasma pTau217 as a marker of Alzheimer tau pathology, not a general neurodegeneration marker.
• Use plasma pTau217 alongside clinical assessment, not as a standalone diagnosis.
• Note which assay and ratio your laboratory reports; they performed slightly differently.
• Consider plasma pTau217 helpful in separating Alzheimer disease from frontotemporal dementia in a memory clinic.

Why it matters

It anchors a blood test now entering memory clinics to the brain pathology it is meant to reflect.

Don't overread it

Thirty-two autopsied patients with established dementia; performance in early or mild disease is not shown here.

The statistics, in plain English

A correlation of about 0.75 is strong: people with higher plasma levels mostly had higher cortical levels. An area under the curve of 0.88 to 0.94 means the test ranked a person with Alzheimer disease above one without it about 9 times in 10. With 32 patients, these estimates carry wide uncertainty.

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