Equivalence of plasma p‐tau217 with cerebrospinal fluid in the diagnosis of Alzheimer's disease

Abstract

AbstractINTRODUCTIONPlasma biomarkers are promising tools for Alzheimer's disease (AD) diagnosis, but comparisons with more established biomarkers are needed.METHODSWe assessed the diagnostic performance of p‐tau181, p‐tau217, and p‐tau231 in plasma and CSF in 174 individuals evaluated by dementia specialists and assessed with amyloid‐PET and tau‐PET. Receiver operating characteristic (ROC) analyses assessed the performance of plasma and CSF biomarkers to identify amyloid‐PET and tau‐PET positivity.RESULTSPlasma p‐tau biomarkers had lower dynamic ranges and effect sizes compared to CSF p‐tau. Plasma p‐tau181 (AUC = 76%) and p‐tau231 (AUC = 82%) assessments performed inferior to CSF p‐tau181 (AUC = 87%) and p‐tau231 (AUC = 95%) for amyloid‐PET positivity. However, plasma p‐tau217 (AUC = 91%) had diagnostic performance indistinguishable from CSF (AUC = 94%) for amyloid‐PET positivity.DISCUSSIONPlasma and CSF p‐tau217 had equivalent diagnostic performance for biomarker‐defined AD. Our results suggest that plasma p‐tau217 may help reduce the need for invasive lumbar punctures without compromising accuracy in the identification of AD.Highlights p‐tau217 in plasma performed equivalent to p‐tau217 in CSF for the diagnosis of AD, suggesting the increased accessibility of plasma p‐tau217 is not offset by lower accuracy. p‐tau biomarkers in plasma had lower mean fold‐changes between amyloid‐PET negative and positive groups than p‐tau biomarkers in CSF. CSF p‐tau biomarkers had greater effect sizes than plasma p‐tau biomarkers when differentiating between amyloid‐PET positive and negative groups. Plasma p‐tau181 and plasma p‐tau231 performed worse than p‐tau181 and p‐tau231 in CSF for AD diagnosis.