Brain volume loss linked to Alzheimer’s treatment may be caused by amyloid plaque removal

A loss of brain volume associated with new immunotherapies for Alzheimer’s disease may be caused by the removal of amyloid plaques, rather than the loss of neurons or brain tissue, a study led by UCL researchers has found.

The research published in Lancet Neurologyanalyzed data from a dozen different trials of amyloid-targeted immunotherapy, including lecanemab, which was recently approved by the UK regulator MHRA.

Although brain shrinkage is usually an unwanted outcome, the team found that the excessive volume loss was consistent across studies and correlated with how effective the therapy was at removing amyloid and was not associated with damage.

As a result, the researchers believe that the removal of amyloid plaques, which are abundant in Alzheimer’s patients, could explain the observed changes in brain volume. And as such, the volume loss should not be a cause for concern.

To describe this phenomenon, the research team has coined a new term: ‘amyloid-removal-related pseudo-atrophy’ or ARPA.

Amyloid-targeted monoclonal antibodies represent a significant therapeutic breakthrough in the treatment of Alzheimer’s disease. These agents work by binding to and causing the removal of amyloid plaques from the brain.

One area of ​​controversy is the effect of these agents on brain volumes. Brain volume loss is a characteristic feature of Alzheimer’s disease, caused by progressive loss of neurons.

Amyloid immunotherapy has consistently shown an increase in brain volume loss, which has raised concerns in the media and medical literature that these drugs could cause unrecognized toxicity to the brains of treated patients.

However, based on the available data, we believe that this excessive volume change is an expected consequence of the removal of pathological amyloid plaques from the brains of patients with Alzheimer’s disease.”

Professor Nick Vos, Senior author and director of the UCL Dementia Research Center

First author, Dr. Christopher Belder (UCL Dementia Research Centre, and the University of Adelaide), said: “We are calling for better reporting of these changes in clinical trials, and for further evaluation to better understand these changes in brain volume as these therapies become more widespread. widely used.”

In August, the Medicines and Healthcare Products Regulatory Agency (MHRA) licensed lecanemab for use in the early stages of Alzheimer’s disease in Britain.

The drug works by targeting beta-amyloid – a protein that builds up in the brains of people with Alzheimer’s disease and is thought to be the trigger that leads to neuronal dysfunction and cell death.

The National Institute for Health and Care Excellence (NICE), which decides whether medicines should be made available through the NHS, has published draft guidance advising that the benefits of lecanemab are too small to justify the costs to the NHS. However, the decision will be reviewed following a public consultation and a second independent committee meeting later this year.