November 15, 2021

expert reaction to mouse study investigating a potential Alzheimer’s vaccine

A study in mice published in Molecular Psychiatry investigates a potential vaccine against Alzheimer’s disease.

Prof Carol Brayne, Professor of Public Health Medicine, University of Cambridge; and Ms Sally Hunter, Research Associate, University of Cambridge, said:

“Most of this study is an analysis of the interaction between a specific peptide and well known anti-abeta antibodies, and behaviour of the peptide in two mouse models. The inclusion of 22 female sporadic AD brain donations and 5 controls (1 female, 4 males) without dementia where selection bias is very likely doesn’t capture or represent the diversity observed in brain collections from whole populations, so its relevance to humans isn’t easy to tease out. The approach used assumes that abeta is the sole driver of dementia in humans, contrary to a robust and longstanding body of evidence gained from studies of dementia in the older human population over many decades, which reveal a complex mix of factors. The implications of this particular finding are therefore uncertain. While the amyloid cascade approach has dominated dementia biomedical research for over 25 years, its relevance to clinical expression of dementia in all its diversity in the human population has never been fully demonstrated. The amyloid cascade hypothesis remains speculative.”

Dr Susan Kohlhaas, Director of Research at Alzheimer’s Research UK, said:

“Ensuring a healthy pipeline of potential new therapies is critical to providing treatment options people with diseases like Alzheimer’s deserve.  Currently there is no disease-modifying treatment available for people with Alzheimer’s in the UK, making drug development even more urgent.

“In this thorough and well-conducted research carried out in mice with features of Alzheimer’s disease, scientists found a vaccine administered through injection found the intended target and helped improve metabolism in brain regions associated with memory and thinking.  Early results in a behavioural task suggest the mice had improved memory and thinking, hinting that this could be a promising new approach, and one that has so far not been tested in Alzheimer’s drugs in clinical trials.

“Like any new drug, this treatment will need to go through a series of clinical trials in people and while this discovery offers hope, this approach is a long way off being proved successful in humans.

“It’s essential that to maintain momentum in dementia research new approaches like this are explored.  We must see continued investment into dementia research to ensure no stone is left unturned when it comes to potential new treatments.  And although this research is still in early stages, with potential new treatments making their way through trials, we must start to prepare the UK’s health system to be ready for new dementia treatments now.”

Prof Tara Spires-Jones, UK Dementia Research Institute at The University of Edinburgh & Deputy Director of the Centre for Discovery Brain Sciences, University of Edinburgh, said:

“This study by Bayer and colleagues shows a vaccine that prevents some Alzheimer’s-like pathologies in mice.  The vaccine causes the immune systems of the mice to react to one of the pathological proteins that clumps in Alzheimer’s disease.  While this study is interesting for the research community, it is important to keep in mind that the findings are from relatively small numbers of mice and we have a long way to go to know whether this approach will be useful for people.”

‘Discovery of a novel pseudo β-hairpin structure of N-truncated amyloid-β for use as a vaccine against Alzheimer’s disease’ by Preeti Bakrania et al. was published in Molecular Psychiatry at 01:00 UK time on Monday 15 November 2021.

Declared interests:

Dr Susan Kohlhaas: “No conflicts.”

Prof Tara Spires-Jones: “I have no conflicts of interest with this study.”

None others received.