Alzheimer's disease: fully automated plasma assays predict brain Aβ status

  • Palmqvist S & al.
  • JAMA Neurol
  • 24 Jun 2019

  • International Clinical Digest
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Takeaway

  • When combined with APOE, fully automated plasma assays for Aβ42 and Aβ40 performed well at predicting β-amyloid (Aβ) positivity of the brain across individuals with differing cognitive status.

Why this matters

  • Need for accurate screening tools for Alzheimer’s disease (AD) in primary care.

Key results

  • In initial cohort, plasma Aβ42 and Aβ40 predicted Aβ status (area under the receiver operating characteristic curve [AUC], 0.80; 95% CI, 0.77-0.83).
  • Small gains seen:
    • When adding APOE (AUC, 0.85; 95% CI, 0.82-0.88).
    • When further adding plasma tau (AUC, 0.86; 95% CI, 0.83-0.88) or both plasma tau and neurofilament light chain (AUC, 0.87; 95% CI, 0.84-0.89).
  • Findings similar regardless of cognitive impairment status, age.
  • In independent validation cohort, plasma Aβ42 and Aβ40 model performed slightly better (AUC, 0.86; 95% CI, 0.81-0.91), but adding plasma tau did not improve on performance.

Expert comment

  • In an editorial, Sid E. O’Bryant, PhD, contends that “… there is a disconnect between the primary care emphasis COU [context of use] and the study design, which was constructed for a blood test of amyloid positivity. The latter is of great use for clinical trials, but no currently available drugs for patient use target amyloid. Therefore, this specific COU is geared more toward clinical trial application than primary care physicians who currently need a test for the presence or absence of AD so currently available treatments and support can be put in place for patients and family members.”

Study design

  • 2 prospective, cross-sectional, multicenter studies among consecutively enrolled participants:
    • Initial cohort: 842 participants (513 cognitively unimpaired, 265 mild cognitive impairment, 64 AD dementia) from Swedish BioFINDER study.
    • Independent validation cohort: 237 participants (34 cognitively unimpaired, 109 mild cognitive impairment, 94 AD dementia) from German biomarker study.
  • Main outcome: performance at predicting brain Aβ positivity (cerebrospinal fluid Aβ42/Aβ40 ratio).
  • Funding: European Research Council; Swedish Research Council; others.

Limitations

  • Missing data for some parameters.
  • Smaller validation cohort.