Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders.
Level 3 - non-randomized controlled study
Multi-cohort cross-sectional diagnostic accuracy study comparing a blood biomarker against neuropathology, PET, and CSF reference standards.
PubMed 32722745 · doi:10.1001/jama.2020.12134
What was done
The study evaluated plasma tau phosphorylated at threonine 217 (P-tau217) as a diagnostic biomarker for Alzheimer disease (AD) across three cross-sectional cohorts: a neuropathology cohort (cohort 1; n=81, 34 with AD and 47 without), the Swedish BioFINDER-2 cohort (cohort 2; n=699, including 301 cognitively unimpaired, 178 mild cognitive impairment [MCI], 121 AD dementia, and 99 other neurodegenerative diseases), and a Colombian autosomal-dominant AD kindred (cohort 3; n=622, 365 PSEN1 E280A mutation carriers and 257 noncarriers). Diagnostic accuracy was assessed against clinical diagnosis, neuropathology, cerebrospinal fluid (CSF) markers, and tau-PET imaging.
What was found
In cohort 1, antemortem plasma P-tau217 differentiated neuropathologically confirmed AD from non-AD with an AUC of 0.89 (95% CI, 0.81-0.97), significantly outperforming plasma P-tau181 and neurofilament light chain (NfL) (AUC range 0.50-0.72; P < .05). In cohort 2, plasma P-tau217 distinguished clinical AD dementia from other neurodegenerative diseases with an AUC of 0.96 (95% CI, 0.93-0.98), outperforming plasma P-tau181, plasma NfL, and MRI measures (AUC range 0.50-0.81; P < .001), with no significant difference compared to CSF P-tau217, CSF P-tau181, or tau-PET (AUC range 0.90-0.99; P > .15). It also differentiated abnormal from normal tau-PET scans with an AUC of 0.93 (95% CI, 0.91-0.96). In cohort 3, P-tau217 was significantly elevated in PSEN1 mutation carriers from age 25 onward, approximately 20 years prior to expected MCI onset.
Why it matters
This demonstrates that a minimally invasive blood test for P-tau217 can identify AD pathology and differentiate it from other neurodegenerative disorders with accuracy comparable to PET scans and CSF lumbar punctures.
Limits
All cohorts were highly selected research or genetic populations rather than routine clinical practice or unselected community samples. The neuropathology cohort had a small sample size (n=81). The study design was cross-sectional, and assay standardization is needed before implementation in clinical care.
Cited by
- supports Blood levels of phosphorylated tau-217 (p-tau217) serve as a biomarker that can detect Alzheimer's disease pathology decades before symptom onset.
- supports Blood levels of phosphorylated tau, specifically p-tau217, strongly correlate with brain amyloid burden and ongoing neuropathology.