Healthcare (Commonwealth Union) – Alzheimer’s disease (AD), a progressive neurodegenerative disorder, remains one of the most challenging health concerns facing our aging population. The accumulation of amyloid plaques, composed primarily of aggregated amyloid-beta (Aβ) peptides, is known to be a key distinguishing factor of AD pathology. As research into this complex disease continues, the understanding of amyloid plaques and their role in Alzheimer’s has evolved. This article delves into the nature of amyloid plaques, their formation, and their significance in the progression of AD.
Given the central role of amyloid plaques in AD, much effort has been directed towards developing therapies targeting the amyloid pathway. A promising area in the treatment of AD has been monoclonal antibodies, such as aducanumab and bapineuzumab, which bind to Aβ peptides and facilitate their clearance from the brain. Another approach involves inhibiting β- and γ-secretases to reduce Aβ production. The clinical trials of many therapies for AD they have yielded mixed results, highlighting the complexity of Alzheimer’s disease and the challenges in developing effective treatments.
A study led by UCL researchers suggests that the reduction in brain volume seen with new immunotherapies for Alzheimer’s disease might result from the clearing of amyloid plaques, rather than the destruction of neurons or brain tissue.
Published in Lancet Neurology, the research examined data from 12 clinical trials involving amyloid-targeting immunotherapies, including lecanemab, recently approved by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).
Although brain shrinkage is typically viewed as negative, the study found that the volume reduction was consistent across trials and closely linked to the effectiveness of plaque removal, with no evidence of harm linked to it.
The findings indicate that the observed brain volume changes may stem from amyloid plaque removal, which is common in Alzheimer’s patients, and should not raise concerns.
The researchers introduced a new term to describe this effect: “amyloid-removal-related pseudo-atrophy” (ARPA).
The Director of the UCL Dementia Research Centre, Professor Nick Fox, pointed out that monoclonal antibodies targeting amyloid are a major advancement in Alzheimer’s disease treatment. These antibodies function by attaching to and initiating the elimination of amyloid plaques within the brain.
“One area of controversy has been 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 – leading to concerns in the media and medical literature that these drugs could be causing unrecognised toxicity to the brains of treated patients.
“However, based on the available data, we believe that this excess volume change is an anticipated consequence of the removal of pathologic amyloid plaques from the brain of patients with Alzheimer’s disease.”
Lead author Dr. Christopher Belder, from the UCL Dementia Research Centre and The University of Adelaide, urged improved documentation of these changes in clinical trials and further investigation to better gain an understanding of the alterations in brain volume as these therapies become more widely used.
In August, the Medicines and Healthcare Products Regulatory Agency (MHRA) approved the use of lecanemab for individuals in the early stages of Alzheimer’s disease in the UK.
Lecanemab functions by targeting beta-amyloid, a protein that accumulates in the brains of people with Alzheimer’s and is believed to play a central role in initiating neuronal damage and cell death.
Draft guidance from the National Institute for Health and Care Excellence (NICE), which evaluates whether treatments should be offered by the NHS, suggests that the benefits of lecanemab do not justify its cost. This recommendation is under review, with a public consultation and a follow-up committee meeting planned for later this year.
