Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care.
Level 2 - randomized trial
Prospective diagnostic accuracy cohort study with an independent reference standard and predefined cutoff values
PubMed 39068545 · doi:10.1001/jama.2024.13855
What was done
A prospective diagnostic accuracy cohort study evaluated a mass spectrometry-based plasma test (amyloid probability score 2 [APS2], combining plasma phosphorylated tau 217 [p-tau217] percentage with amyloid-β 42:40 ratio) across 1,213 patients with cognitive symptoms in Sweden between 2020 and 2024. Predefined biomarker cutoffs from an independent cohort were applied to batch-analyzed cohorts (primary care n = 307; secondary care n = 300) and prospectively analyzed biweekly cohorts (primary care n = 208; secondary care n = 398). The reference standard for Alzheimer disease (AD) pathology was cerebrospinal fluid Aβ42:Aβ40 and p-tau217.
What was found
Overall, 50% of patients had AD pathology (mean age 74.2 years, 48% women). APS2 achieved an AUC of 0.97 (PPV 91%, NPV 92%) in batch primary care and 0.96 (PPV 88%, NPV 87%) in batch secondary care. In prospective testing, APS2 yielded an AUC of 0.96 (PPV 88%, NPV 90%) in primary care and 0.97 (PPV 91%, NPV 91%) in secondary care, with diagnostic accuracy ranging from 88% to 92% across cohorts. Primary care physicians achieved 61% diagnostic accuracy (95% CI, 53%–69%) for clinical AD versus 91% (95% CI, 86%–96%) using APS2; dementia specialists achieved 73% (95% CI, 68%–79%) versus 91% (95% CI, 88%–95%) using APS2. Diagnostic accuracy for percentage p-tau217 alone was identical to APS2 (90% [95% CI, 88%–91%] vs 90% [95% CI, 88%–92%]).
Why it matters
A blood test based on plasma p-tau217 accurately identifies AD pathology in routine primary care and specialist settings, markedly outperforming standard clinical assessments and offering a minimally invasive alternative to CSF lumbar punctures.
Limits
The study was conducted entirely in Sweden, limiting geographic and ethnic generalizability. The test was evaluated only in symptomatic individuals seeking clinical evaluation, not as a screening tool in asymptomatic populations. The impact of blood biomarker results on clinical management and patient outcomes was not assessed.
Cited by
- supports Blood levels of phosphorylated tau, specifically p-tau217, strongly correlate with brain amyloid burden and ongoing neuropathology.