October 7, 2025

expert reaction to study of amyloid-β clearance in a mouse model of Alzheimer’s Disease

A study published in Signal Transduction and Targeted Therapy looks at amyloid-β clearance in a mouse model of Alzheimer’s Disease.

Dr Íris Luz Batalha, Senior Lecturer (Associate Professor) and Group Leader, University of Bath, said:

“Alzheimer’s disease (AD) is the most common form of dementia, affecting 1 in 14 people over the age of 65. It’s a devastating disease for both patients and their families, essentially robbing people of their essence: their memories, feelings, independence, and ability to think and move. Unfortunately, despite huge efforts from the pharma industry, we are still in the process of fully understanding the disease and finding truly disease-modifying treatments. It’s known that protein aggregation in the brain (specifically, amyloid-beta and tau proteins) is strongly associated with AD. This research offers a completely new approach that uses nanoparticles to target another protein (LRP1), which is located in the cells of the blood-brain barrier, to induce a specific natural mechanism that removes amyloid-beta from the brain, thereby effectively improving memory, cognition, and learning capabilities.

“Any animal model will always be limited in its translational capacity. However, until we find better models, they are still the best we have to try to mimic human disease. Researchers in this study used a double-transgenic mouse model that shows increased expression of amyloid-beta. It is a good model to study the amyloid-beta pathology, but of course, it does not completely mimic the human disease. In the future, the team will certainly have to test these nanoparticles in large non-rodent animal models to fully understand efficacy and toxicology. And, in this case, there are also additional regulatory hurdles to address, as these are a new class of therapeutic agents (targeted polymeric nanoparticles). However, the field of nanotechnology has been advancing tremendously since the COVID-19 pandemic, and I believe these are all hurdles that can be surpassed.

“I think this is really exciting because it gives us new insights into novel therapeutic strategies for a disease that basically has no really good treatment available. Over the last decades, pharmaceutical companies saw many clinical trials in AD failing, but the truth is that the landscape seems to be changing with the recent approvals of anti-amyloid monoclonal antibodies. All of these approved treatments were also tested in animal models.

“All scientific research has limitations, as we are investigating unexplored territory. However, this is how science advances: little by little, we build our castles. Little by little, we learn more about diseases that affect human life, develop new treatments, and help people live longer and better lives. Science is not for scientists. It’s for everyone.”

Prof Tara Spires-Jones, Director of the Centre for Discovery Brain Sciences at the University of Edinburgh, Group Leader in the UK Dementia Research Institute, and Past President of the British Neuroscience Association said:

“As a researcher working in the Alzheimer’s field, I would not call this study a breakthrough.  This study in mice uses nanoparticles to target a protein called LRP1 to promote removal of toxic amyloid beta from the brain.  While the idea of facilitating amyloid beta clearance is interesting and potentially useful, these experiments had several serious limitations. Studies were performed in only a few mice per experiment (3 per group for many experiments). Further, the statistical tests used in the study were not always appropriate, counting multiple measures from the same animal as independent when they are related because they come from the same animal (called statistical pseudoreplication).  The mouse model used over expresses two familial Alzheimer’s disease associated genes and does not recapitulate the full spectrum of human disease pathology, and importantly the mouse brain and vasculature are not exactly the same as humans.  While the idea is interesting, these findings need replication and are a very long way from helping people living with Alzheimer’s disease.”

Dr Julia Dudley, Head of Research, at Alzheimer’s Research UK says

“In Alzheimer’s disease, the protective blood brain barrier can become less effective, causing damage to the brain. This study showed that using nanoparticles to restore the effective functioning of the blood brain barrier resulted in the removal of amyloid from the brain in mice. It adds to the growing evidence that repairing the blood brain barrier itself could offer a new way to treat Alzheimer’s. 

“It’s too early to say if this method will work in people with Alzheimer’s. This study was carried out in mice, so there will be differences in how the disease develops in people. Future research will need to test whether this approach could be effective in treating people with Alzheimer’s.

“With over 1 million affected by dementia in the UK, we urgently need to find new treatments for Alzheimer’s and other diseases that cause dementia. If we are to treat dementia in the future, we will need a host of different treatments targeting different aspects of the disease.  This type of research – while still early – is crucial for taking us closer to finding a cure.”

Prof Francesco Aprile, Associate Professor in Biological Chemistry, Imperial College London’s Department of Chemistry, said:

“The blood-brain barrier protects the brain, but it also makes drug delivery and waste removal more difficult. In this mouse study, researchers reprogram a natural export pathway to help clear amyloid-β from the brain. It is quite innovative because instead of simply trying to push drugs in, they enhance one of the brain’s natural pathways to more efficiently remove Alzheimer’s toxic proteins.

“This is an innovative early-stage approach with encouraging results in mice. The rapid clearance of amyloid and the behavioural improvements are particularly striking. As with any preclinical study, further testing, including safety studies and validation in larger models, will be critical before considering human trials.

“This study stands out because it clears amyloid within hours and restores memory-like behaviour for months after only a few doses. Of course, promising results in mice do not always carry over to people. Many past approaches have looked effective in mouse models but failed to show meaningful benefits in clinical trials. Still, the strength and speed of the effects here make this a particularly noteworthy preclinical finding.

“This is research done in mice, not in humans. The results are encouraging, but the approach still needs more testing, especially to check safety and effectiveness in larger animals before any human trials can begin.”

‘Rapid amyloid-β clearance and cognitive recovery through multivalent modulation of blood–brain barrier transport’ by Junyang Chen et al. was published in Signal Transduction and Targeted Therapy 

DOI: https://doi.org/10.1038/s41392-025-02426-1

Declared interests

Dr Iris Luz Batalha: Dr Iris Luz Batalha has previously worked with some of the authors of this study but was not directly involved in this study

Prof Tara Spires-Jones: I have no conflicts with this study but have received payments for consulting, scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, and Eisai, and direct a company Spires-Jones Neuroscience, Ltd to act as a consultant. I am also Charity trustee for the British Neuroscience Association and the Guarantors of Brain and serve as scientific advisor to several charities and non-profit institutions.

For all other experts, no reply to our request for DOIs was received.