AI Summary
This personal view discusses brain volume changes following anti-amyloid β immunotherapy for Alzheimer's disease. While progressive cerebral volume loss is a hallmark of the disease, participants in immunotherapy trials experienced excess volume loss despite the prediction that treatments would slow loss. The excess volume changes are specific to therapies that reduce amyloid β levels, potentially related to plaque removal rather than harmful effects.
Progressive cerebral volume loss on MRI is a hallmark of Alzheimer’s disease and has been widely used as an outcome measure in clinical trials, with the prediction that disease-modifying treatments would slow loss. However, in trials of anti-amyloid immunotherapy, the participants who received treatment had excess volume loss. Explanations for this observation range from reduction of amyloid β plaque burden and related inflammatory changes through to treatment-induced toxicity. The excess volume changes are characteristic of only those immunotherapies that achieve amyloid β lowering; are compatible with plaque removal; and evidence to date does not suggest an association with harmful effects.