Alzheimer’s disease, amyloid and ethics

15 February 2023

Abstract

George Winter looks at the developments that have been and still must be made in Alzheimer’s disease and the ethical considerations that must be considered alongside these developments

In November 2022, van Dyck et al (2022) reported the results of an 18-month, double-blind, phase 3 trial of 1795 participants with early Alzheimer’s disease and evidence of amyloid. Half received lecanemab, a monoclonal antibody that binds to soluble amyloid-beta (Aβ) protofibrils. Lecanemab reduced amyloid markers, giving ‘moderately less decline on measures of cognition and function than placebo at 18 months but was associated with Alzheimer’s disease adverse events’ (van Dyck et al, 2022).

Although media outlets hailed the results as ‘historic… lecanemab made a tiny difference to cognitive deterioration on cognitionto cognitive deterioration on cognition scales over 18 months, which although statistically significant may not be clinically significant’ (Kmietowicz, 2022). Perhaps tempering media-fuelled expectations, Adhikari et al (2022) considered amyloid-related imaging abnormalities (ARIA) among some Alzheimer’s disease participants who received therapeutic anti-Aβ antibodies. The authors noted that the molecular mechanisms behind ARIA remain undefined; and identified ‘many allergy-related proteins involved in pro-inflammatory responses and endothelial dysfunction …’

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