Modelling disease in Alzheimer's research

The BBC News headline Alzheimer's research 'needs new strategy' is certainly eye catching, and you won't find us arguing that the lack of new therapies emerging from Alzheimer's research in the previous decades has been disappointing. However, is a switch from animal models to human studies really the whole story?

The use of animal models for disease research should never be undertaken lightly, both due the ethical considerations but also the differences between species which means that results based on experiments in animals may not be relevant in humans. As the article obliquely refers, developments now means that there are a variety of different techniques to look at the living human brain that can a yield a wealth of information. Such studies are undoubtedly valuable to Alzheimer's research, but have their own limitations. For instance, they can provide lots of information on electrical patterns and tissue density, but are less use for looking at biochemical changes and alterations in gene expression.

Also, due to the technical problems of working on whole brains, researchers have already been using cell cultures in their work for many of years. Improving the relevance of the cells used, human rather than animal, can only be a good thing. But again, there are limitations with these techniques. Isolating cells and then manipulating them to reproduce and stay alive in culture can lead to changes that are not reflective of their natural state. In addition, it loses the complex interactions between multiple cell types that happen in the whole organism.

What is not addressed by this article though are two very large reasons why Alzheimer's research has not yielded the progress we would have hoped at this point in time.

The first is money; Alzheimer's research is very much the poorer cousin of cancer and heart disease. Less money, equals less research, equals less progress.

The second issue was less obvious until very recently, which is that a lot of clinical trials for therapeutics were conducted after symptoms of Alzheimer's first appear. However, recent research has started to reveal that the changes that lead to the development of Alzheimer’s disease can start years before symptoms show. The current attempts to treat the symptoms could just be too little too late, like trying to stop a run-away car when it has already hurtled half way down the hill - much better to catch the car when it is just starting to move. However, before we can do this, we need a way of catching Alzheimer’s earlier and this will require new diagnostic tools such as blood tests that detect the earliest changes (a number of these tests are already in development).

So, yes, a careful appreciation of the limitations of animal models and an eye on new techniques for human studies can only be a good thing, but this is only one part of a much wider story.