Reducing ARIA risk in Alzheimer's disease: Real-world impact of APOE genotype-guided slow titration with aducanumab and lecanemab

J Alzheimers Dis. 2025 Oct;107(4):1400-1403. doi: 10.1177/13872877251366657. Epub 2025 Aug 13.

Abstract

We evaluated whether apolipoprotein E (APOE) genotype-guided slow titration of monoclonal antibodies reduced amyloid-related imaging abnormalities (ARIA) in Alzheimer's disease. We retrospectively analyzed ARIA incidence in 25 patients on aducanumab and 19 patients on lecanemab on a genotype-informed protocol in a private practice setting. ARIA-E and ARIA-H each occurred in 4% of the aducanumab group and 5% of the lecanemab group. Plaque clearance was achieved in 50% of evaluable aducanumab patients and 26.3% of lecanemab patients. Compared to clinical trial ARIA rates, our results suggest that individualized, genotype-informed titration improves safety although plaque clearance rates were less robust.

Keywords: APOE genotype; Alzheimer's disease; aducanumab; amyloid-related imaging abnormalities; lecanemab; monoclonal antibodies; real-world evidence; slow titration.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / genetics
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Apolipoproteins E* / genetics
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Plaque, Amyloid* / diagnostic imaging
  • Plaque, Amyloid* / drug therapy
  • Retrospective Studies

Substances

  • aducanumab
  • Antibodies, Monoclonal, Humanized
  • Apolipoproteins E