April 6, 2023

expert reaction to deep brain stimulation in mouse model of Alzheimer’s disease

A study published in Cell Stem Cell looks at the use of deep brain stimulation in a mouse model of Alzheimer’s disease.

Dr Sara Imarisio, Head of Strategic Initiatives at Alzheimer’s Research UK, said:

“Although drugs that directly remove amyloid plaques, like lecanemab, are showing promise in treating Alzheimer’s disease, we also need approaches that work in other ways. This will include treatments that protect nerve cells from damage, and ways to restore brain functions lost during the disease’s development.

“This study discovered a technique to stimulate new nerve cell growth in mice with Alzheimer’s-like symptoms. By using a combination of light pulses and exposure to nerve-stimulating chemicals, the researchers were able to activate specific nerve cells deep in the brain, partly restoring memory and emotional functions.

“It’s important to note that these results are in mice, and there are differences between mouse and human brains. And while these findings provide a promising lead for investigating potential new approaches for treating Alzheimer’s in humans, it’s a very long way from practical application.

“Nevertheless, studies like these are essential to unravel the complexities of Alzheimer’s, and bring us closer to ways to effectively treat, and even cure, the disease.”

Prof Malcolm Macleod, Professor of Neurology and Translational Neuroscience, University of Edinburgh, said:

“This study is potentially of interest, but there are some problems with the presentation by the authors, and some problems with the methods used. 

“Specifically, on the presentation, the title says that the intervention “restores cognitive and affective function in Alzheimer’s disease”, but this is to overstate things. Mice do not get Alzheimer’s, although scientists can model some of the features in certain animal models, as presented here. But these do not capture the whole story of what Alzheimer’s does to humans, and we know of many interventions which appear to improve outcome in these (imperfect) animal models but which have no effect in humans.

“The study does not report the random allocation of animals to experimental groups; this is an important study design feature which helps ensure that groups are balanced, and that any differences observed are due to the intervention, and not to some other phenomenon. It has been standard in clinical trials for decades, and recommended for animal studies for over 10 years.

“Next, the number of animals used is fairly low, which again brings the conclusions into question. They say they based the numbers of animals used on previous experiments, but we know that experiments in the neurosciences are substantially under-powered (ie too small reliably to detect the effects they report), and so doing it this way because that’s how we have always done it is problematic.

“Two further observations: many authorities consider the forced swim test to be a poor measure of depression like behaviours, and there have been recommendations that alternative approaches are used; and the statement that data are available “on reasonable request” is a very poor substitute for placing the data in a publicly available repository (as indeed they did with their proteomics data).”

‘Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer’s disease’ by Ya-Dong Li et al. was published in Cell Stem Cell at 16:00 UK time on Thursday 6^th April.

DOI: https://doi.org/10.1016/j.stem.2023.02.006

Declared interests

Prof Malcolm Macleod: “I have no conflicts of interest to disclose.”

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