The problem with animal experiments in Alzheimer’s disease research

In the human brain, Alzheimer’s disease is characterised by an abnormal build-up of the proteins amyloid (forming “plaques” around the brain cells) and tau (forming “tangles” within the brain cells). Animals don’t naturally develop Alzheimer’s disease, but even genetically modified animals fail to replicate both the amyloid plaques and tau tangles that define this disease in humans. Therefore, using animal experiments to study Alzheimer’s disease can lead to misleading results, causing drugs to fail in human trials despite successful results in pre-clinical testing. Despite these widely acknowledged issues, thousands of animals are still used each year in Alzheimer’s disease research, without bringing us closer to a cure.

A complex human cell model

To move beyond flawed animal experiments, Dr Patricia Ragazzon at Keele University, alongside her collaborators at the University of Salford and University of Manchester, is developing a new human cell culture model of the brain. This model includes three different brain cell types grown together in a method known as ‘co-culture’, replicating the human brain environment where many different cell types work together to carry out normal processes (Figure 1).

The three types of human brain cells used in the model are neurons (cells that send messages to the body to allow it to carry out its functions), astrocytes (star-shaped cells that carry out ‘housekeeping’ functions in the brain and central nervous system) and microglia (immune cells of the brain) (Figure 2). These different cell types increase the complexity and versatility of the model, allowing it to be used to study Alzheimer’s disease development and progression.

The danger of stress

Dr Ragazzon is interested in how stress and inflammation can affect the brain cells in Alzheimer’s disease. Using her co-culture model, she will investigate how stress affects the development of tau tangles, one of the key features of Alzheimer’s disease. By adding the chemicals TBHP and formaldehyde to induce stress in the cells, changes in tau tangles and an increase in amyloid plaques can be observed, simulating advanced Alzheimer’s disease stages where symptoms become more problematic.

Severe stress causes cells to die and release toxins into their environment, which can cause stress to neighbouring cells, creating a harmful cycle of stress, inflammation and cell death. This, combined with increased numbers of tau tangles and amyloid plaques, could drive Alzheimer’s disease progression. If Dr Ragazzon’s model confirms these effects, it could provide some much-needed insight into the some of the current mysteries of Alzheimer’s disease development.

Sharing animal-free methods for Alzheimer’s disease research

This project builds on two previous Animal Free Research UK Summer Studentships (Patricia Bailey, 2022 and Imogen Carmichael, 2021), where animal-free cell culture methods were tested and optimised.

This versatile human cell model has many potential research uses as it is complex enough to allow us to study important brain cell processes, while still being user-friendly. Importantly, the methods don’t require any expensive or complicated equipment, making them accessible to researchers worldwide.

Dr Ragazzon plans to share her methods and findings with the scientific community through conferences, publications and a workshop for the pharmaceutical industry and other researchers, promoting the uptake of animal-free research techniques. If widely adopted, Dr Ragazzon’s methods could save thousands of animals from being used in Alzheimer’s disease research each year, while providing valuable human-relevant data.