Brain in a Dish Provides New Way to Learn About Alzheimer’s

Summary: Researchers report they have discovered a new method to replicate one of the earliest changes in Alzheimer’s disease.

Source: Babraham Institute.

Researchers at the Institute have found a way to replicate one of the earliest changes in Alzheimer’s disease in a dish. This means that it should now be possible to find out a lot more about why it happens – and how to stop it. The new findings are published in the journal Molecular Neurodegeneration and supported by the charity Alzheimer’s Research UK.

Currently, there are no effective treatments to slow or stop Alzheimer’s disease, only ones that aim to manage the disease’s symptoms. This is due in part to difficulty in identifying the first physical signs of the disease in its early stages. Early treatment is an important goal as it could prevent the irretrievable loss of nerve cells seen as the disease progresses.

Being able to properly understand what is happening in the brain as a result of Alzheimer’s disease requires an accurate and accessible system. Until now, much research has relied on post-mortem brain samples, either from people who have passed away with the disease or from mice bred to show features of Alzheimer’s.

Researchers at the Institute have used a method to sustain brain slices from mice in the laboratory. The advantage of these brain slices is that they retain a 3D structure, containing the many different types of cell found in the living brain. The brain slices can survive for several weeks, allowing longer-term studies into what happens to a brain affected by Alzheimer’s, and they can be imaged in real time, sampled and manipulated by the addition of drugs.

The team used the technique to study one of the earliest and most clinically relevant changes in human Alzheimer’s disease which is the loss of synapses – the connection points between nerve cells that allow them to communicate with each other. The brain slices the team studied were taken from young mice bred to develop features of Alzheimer’s disease and contained the hippocampus, a key part of the brain that is important for memory and is affected by the disease. The researchers were able to observe a build-up of the hallmark Alzheimer’s protein amyloid in the slices over time, gaining important insights into how this increase is associated with a loss of proteins in the synapses responsible for transmitting signals between nerve cells. They were also able to treat the slices with a drug to effectively modify the amount of amyloid protein they produced, highlighting the future value of this approach for testing potential new Alzheimer’s treatments.

Image shows mouse brain slices in a petri dish.
Mice brain clices maintained in a petri dish to allow study of the earliest stages of Alzheimer’s disease. Credit: The researchers.

Claire Harwell, a PhD student at the Babraham Institute and first author on the paper, said: “This technique will help us to observe the earliest, usually hidden, stages of Alzheimer’s disease whilst providing an accessible system for the identification of promising treatments. For effective therapeutics to be developed, we must understand and target the disease at its earliest stages.”

The method reduces the numbers of animals required to undertake this type of research and means that researchers can study important stages in the disease process without the mice themselves experiencing disease symptoms. It also allows researchers to study live brain tissue and learn how it reacts to drugs in a way that isn’t possible with living humans or mice.

Professor Michael Coleman, research group leader at the Babraham Institute and Professor of Neuroscience at the John van Geest Centre for Brain Repair, explained: “The value of the system is that candidate drugs can be readily delivered and the effects monitored, thus filling a vital gap between cell culture and animal studies. We expect that this approach will be extremely useful in research into Alzheimer’s disease and potential treatments.”

Image shows brain slices.
This image compares brain slices from a healthy mouse (left panel) and a mouse with Alzheimer’s disease mutations (right panel). The brain sections have been labelled with fluorescent staining to identify synapses (shown as red). Comparing the images shows that synapses are reduced in mice brains that contain Alzheimer’s disease mutations, modelling what is known to happen in a human brain affected by Alzheimer’s. These images show brain slices cultured for six weeks. Image details: x60 magnification, red= synapses (synaptophysin), green= nerve cell axons (tau). image is credited to the researchers.

Dr Simon Ridley, Director of Research at Alzheimer’s Research UK, said: “To develop new treatments for people with Alzheimer’s we need a better understanding of the disease and how it affects the brain. The brain is a very inaccessible organ, presenting researchers with a unique challenge, particularly when studying the very early stages of diseases like Alzheimer’s. It’s important for scientists to use a range of approaches to understand different aspects of Alzheimer’s and this new research provides a window into some of the early stages of the disease process. Research such as this has the power to open new doors to studies in humans and to help in the search for new treatments for this devastating disease.”

About this Alzheimer’s disease research article

Funding: This work was supported by Alzheimer’s Research UK. The Babraham Institute is strategically funded by the Biotechnology and Biological Sciences Research Council.

Animal research statement: As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research presented here used brains from mice in order to study the changes associated with the onset of Alzheimer’s disease.

All animal work was approved by the Babraham Institute Animal Welfare and Ethical Review Body and UK Home Office, and carried out in accordance with the Animals (Scientific Procedures) Act, 1986, under a Project Licence. In evaluating any research using animals, the Institute applies the principles of reduction, refinement and replacement. One of the benefits of this study is to provide new methods for this.

Source: Laurie Callahan – Babraham Institute
Image Source: This images are credited to the researchers.
Original Research: Full open access research for “Synaptophysin depletion and intraneuronal Aβ in organotypic hippocampal slice cultures from huAPP transgenic mice” by Claire S. Harwell and Michael P. Coleman in Molecular Neurodegeneration. Published online June 10 2016 doi:10.1186/s13024-016-0110-7

Cite This Article

[cbtabs][cbtab title=”MLA”]Babraham Institute. “Brain in a Dish Provides New Way to Learn About Alzheimer’s.” NeuroscienceNews. NeuroscienceNews, 14 June 2016.
<>.[/cbtab][cbtab title=”Babraham Institute”]Babraham Institute. (2016, June 14). Brain in a Dish Provides New Way to Learn About Alzheimer’s. NeuroscienceNews. Retrieved June 14, 2016 from[/cbtab][cbtab title=”Chicago”]Babraham Institute. “Brain in a Dish Provides New Way to Learn About Alzheimer’s.” (accessed June 14, 2016).[/cbtab][/cbtabs]


Synaptophysin depletion and intraneuronal Aβ in organotypic hippocampal slice cultures from huAPP transgenic mice

To date, there are no effective disease-modifying treatments for Alzheimer’s disease (AD). In order to develop new therapeutics for stages where they are most likely to be effective, it is important to identify the first pathological alterations in the disease cascade. Changes in Aβ concentration have long been reported as one of the first steps, but understanding the source, and earliest consequences, of pathology requires a model system that represents all major CNS cell types, is amenable to repeated observation and sampling, and can be readily manipulated. In this regard, long term organotypic hippocampal slice cultures (OHSCs) from neonatal amyloid mice offer an excellent compromise between in vivo and primary culture studies, largely retaining the cellular composition and neuronal architecture of the in vivo hippocampus, but with the in vitro advantages of accessibility to live imaging, sampling and intervention.

Here, we report the development and characterisation of progressive pathological changes in an organotypic model from TgCRND8 mice. Aβ1-40 and Aβ1-42 rise progressively in transgenic slice culture medium and stabilise when regular feeding balances continued production. In contrast, intraneuronal Aβ continues to accumulate in close correlation with a specific decline in presynaptic proteins and puncta. Plaque pathology is not evident even when Aβ1-42 is increased by pharmacological manipulation (using calpain inhibitor 1), indicating that soluble Aβ species, or other APP processing products, are sufficient to cause the initial synaptic changes.


Organotypic brain slices from TgCRND8 mice represent an important new system for understanding mechanisms of Aβ generation, release and progressive toxicity. The pathology observed in these cultures will allow for rapid assessment of disease modifying compounds in a system amenable to manipulation and observation.

“Synaptophysin depletion and intraneuronal Aβ in organotypic hippocampal slice cultures from huAPP transgenic mice” by Claire S. Harwell and Michael P. Coleman in Molecular Neurodegeneration. Published online June 10 2016 doi:10.1186/s13024-016-0110-7

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