Strong diagnostic performance of plasma ptau217 for CSF biomarker-defined young-onset Alzheimer disease in a diagnostically heterogeneous clinical cohort

J Neurol. 2024 Dec 12;272(1):25. doi: 10.1007/s00415-024-12732-3.

Abstract

Objective: We investigated diagnostic utility of phosphorylated tau 217 and 181 (ptau217, ptau181), glial fibrillary acidic protein (GFAP), amyloid beta 42 and 40 (Aβ42, Aβ40), and neurofilament light (NfL) to distinguish biomarker-defined Alzheimer disease (AD) from non-AD conditions, in a heterogenous clinical cohort of younger people.

Methods: Plasma biomarkers were analysed using ultrasensitive technology, and compared in patients with CSF Alzheimer disease profiles (A+T+) to other CSF profiles (Other).

Results: Seventy-nine patients were included, median age 60.8 years: 16 A+T+, 63 Other. Ptau217, ptau181, GFAP were significantly elevated in A+T+ compared to Other (3.67 vs 1.12 pg/mL, 3.87 vs 1.79 pg/mL, 189 vs 80 pg/mL, respectively). ptau217 distinguished AD from Other with 90% accuracy (88% specificity, 100% sensitivity). ptau217 also demonstrated strong diagnostic performance for clinically diagnosed AD.

Conclusions: Plasma ptau217 has strong diagnostic performance in distinguishing CSF biomarker-defined AD in a clinically relevant, younger cohort of people with symptoms, adding further weight for a simple diagnostic blood test for AD as a cause of a patient's symptoms.

Keywords: Alzheimer’s disease; Biomarker; Dementia; Diagnosis; ptau217.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / diagnosis
  • Amyloid beta-Peptides* / blood
  • Amyloid beta-Peptides* / cerebrospinal fluid
  • Biomarkers* / blood
  • Biomarkers* / cerebrospinal fluid
  • Cohort Studies
  • Female
  • Glial Fibrillary Acidic Protein / blood
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid
  • Humans
  • Male
  • Middle Aged
  • Neurofilament Proteins* / blood
  • Neurofilament Proteins* / cerebrospinal fluid
  • Peptide Fragments / blood
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Sensitivity and Specificity
  • tau Proteins* / blood
  • tau Proteins* / cerebrospinal fluid

Substances

  • tau Proteins
  • Biomarkers
  • Amyloid beta-Peptides
  • Neurofilament Proteins
  • neurofilament protein L
  • Glial Fibrillary Acidic Protein
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • GFAP protein, human
  • amyloid beta-protein (1-40)