Can breaking down brain plaques prevent Alzheimer's?

Brain plaques are a hallmark of Alzheimer’s disease (AD) and the degree of brain plaque correlates with the severity of the disease. However, it is thought that the plaques are an end product of the brain damaging process, and not the cause. 

A recent drug trial demonstrated that a monoclonal antibody drug called Lecanemab was able to break down amyloid plaques in patients with established mild Alzheimer’s disease and this slowed progression of the disease. 

This is the first trial of a plaque targeting monoclonal antibody (MAB) to show a positive outcome. There are several proposed reasons for why this particular trial was successful whereas other similar trials were not. In this trial only people with mild AD were included. It is thought that plaque clearing MABs will not work in patients with more severe disease as extensive and irreversible damage has already taken place. Another reason is that the MAB used in this trial targeted the toxic intermediates as opposed to the plaques themselves, whereas other MABs have targeted the latter. Finally, this trial reduced amyloid levels more effectively and quicker than other trials.

However, this trial does raise some questions. Although amyloid plaque was reduced to a very low level the symptomatic effects were very small during this 18-month trial. This mismatch highlights our lack of understanding of the pathogenesis behind AD. Perhaps there are other processes in AD that are more important than amyloid plaque formation, alternatively, there may be a time-delay for cognitive changes to be seen. 

It is yet to be determined whether giving this MAB to people without established brain plaques could prevent Alzheimer’s disease and, like all drugs, this may come with some risks. 

In summary, as breaking down plaques in individuals with mild AD results in some modest delay in memory decline and symptoms, it may well be the case that breaking down plaques in individuals without AD may prevent it altogether - however more research is needed to demonstrate this.