Amyloid and tau; partners in crime

Memory loss can be, for many families, the first sign that a loved-one is developing dementia. It is the most well-known symptom of Alzheimer’s disease, and often very distressing. But how are memories formed? And how does Alzheimer’s alter the way we remember?

How are memories formed?

The number of nerve cells in our brains does not increase dramatically over our lifetime. This means that for new information to be stored there must be changes in the way that nerve cells communicate with each other. Imagine a nerve cell as an arm with a clenched fist. It can communicate with just one other neighbouring nerve. However, as the nerve cell receives new information, it grows ‘fingers’ known as dendrites. These dendrites help the nerve cell communicate with many other neighbouring nerve cells, forming new pathways in response to different environmental triggers, such as new faces or new smells. In order for a memory to form, information received by our starting nerve cell must always follow the same path to its neighbours. 

Memory loss in dementia

In Alzheimer’s and other causes of dementia, the pathways underlying memory formation are altered. Understanding how these processes are damaged is an important part of the research that we fund. For many years it has been widely accepted that the build-up of a protein called amyloid into ‘plaques’ is the key culprit in Alzheimer’s. The accumulation of plaques can lead to nerve cell damage, meaning a loss of connections. In regions of the brain associated with memory formation, nerve cell destruction causes the symptoms that are so distressing for people with dementia. The build-up of amyloid can also prevent the strengthening of connections between nerve cells, making it hard for new memories to form.

Amyloid plaques no longer hog the limelight

However, over recent years, this theory for the progression of Alzheimer’s has been questioned. Research has shown that the link between the number of amyloid plaques and loss of memory and thinking is not always simple. Some people with a large number of amyloid plaques in their brain may have no trouble with memory tasks, whilst others have great difficulties. So while amyloid build-up is a hallmark of Alzheimer’s, it is clearly not the whole story.

Bring on the tau researchers. Tau is another hallmark protein found in Alzheimer’s disease. Normally, it serves an important role in nerve cells, forming part of the scaffolding that spans the long nerve cell bodies. Tau also helps the transport of biological molecules from one end of the cell to the other. When tau is abnormal, it forms tangles, causing transport to go awry. This can disrupt communication between nerve cells because the biological molecules needed for communication are not in the right place at the right time. The contribution of tau to Alzheimer’s has for many years been poorly understood, so understanding the protein in more detail is a key strand of our Research Strategy at Alzheimer’s Research UK. That’s also why we’re helping to sponsor the CRACKIT UnTangle initiative, a funding scheme to aid scientists solve the tau puzzle.

However, working out the individual roles of tau and amyloid in Alzheimer’s progression may not provide that eureka moment for disease treatment. As highlighted in a recent article by one of our funded scientists, it is likely that it will be the contribution of both proteins that sheds light on how best to tackle the disease.

Dr Tara Spires-Jones, form the University of Edinburgh, has published an overview of our current knowledge about tau and amyloid, and how they act to disrupt nerve cell function and memory formation. She has highlighted some key studies that have taken place over recent years suggesting that amyloid and tau work together to cause the destruction seen in Alzheimer’s.

Perhaps the biggest indicator that amyloid alone does not drive Alzheimer’s is that problems with memory and thinking are strongly linked to the amount of abnormal tau. So while there is no clear relationship between the amount of amyloid and a person’s ability to think, there is a very clear link between the amount of tau and these symptoms. Interestingly, several studies suggest that tau may need to be present for amyloid to have its toxic effects on nerve cells. Removing the tau could make amyloid harmless. Clearly the two proteins are partners in crime in the destruction of nerve cells.

Scientists researching Alzheimer’s disease have made huge progress in understanding the steps that lead to dementia. However, more research needs to be carried out so we can work out how best to target these pathways for treatment. Hopefully the work of Dr Spires-Jones and others will get us to that point sooner!