Endocytosis and Alzheimer’s disease

In collaboration with Dr Rhian Thomas and Professor Mark Good.

What are the aims of this group?

Dr Kidd’s research concentrates on cellular and molecular pharmacology to understand more about the mechanisms underlying Alzheimer’s disease, with the ultimate aim of developing new therapies for this condition.

What do we already know?

Alzheimer’s disease is likely to develop as a result of many contributing factors. The main risk factor is increasing age, but we still do not understand how this leads to the disease.

Endocytosis is the process whereby cells actively take up items from their surrounding environment. Changes in endocytosis occur in Alzheimer’s disease – the process is central to the production of amyloid-β, the main component of the amyloid plaques found in the brains of Alzheimer’s patients. These changes have been identified in patients’ brains and also as susceptibility genes which give a small, increased risk of developing Alzheimer’s disease.

What are they trying to find out?

Dr Kidd’s group have been looking at how changing the expression of endocytic proteins affects cellular processes and may therefore contribute to the development of Alzheimer’s disease. They have shown that altering proteins involved in each of the two main types of endocytosis (clathrin-dependent and caveolin-dependent) has contrasting effects on the levels of a number of proteins implicated in the pathogenesis of Alzheimer’s disease.

They have also been examining how the expression of endocytic proteins is affected by ageing in mouse and human brains, to see if changes in the expression of these proteins may predispose individuals to Alzheimer’s disease. They have found that clathrin levels are increased in cognitively healthy older men (aged 70-85) compared to young (aged 20-30) and middle-aged men (aged 40-50). Interestingly, no changes were seen in clathrin levels in mice of different ages. They will go on to compare these results to those using tissue from people with Alzheimer’s disease.

How do they do this?

The group uses a variety of human cell lines, animal models and human tissue and many biochemical and molecular biological techniques to investigate cell function.

Why is it important?

Understanding more about how manipulations of endocytosis can affect key proteins in Alzheimer’s disease is critical to elucidating how the disease could be caused. The group’s findings have already suggested key parts of the pathways which could be altered in the disease and are helping to explain some of the genetic susceptibility data. Furthermore, their research could identify novel targets which could be used to develop new drugs to treat Alzheimer’s disease.

The work on ageing is novel with the potential to highlight stages in the lifespan of man when therapeutic interventions would be beneficial to slow or halt the development of Alzheimer’s disease. Interestingly, their data show clearly that there are differences between humans and mouse models of Alzheimer’s disease, which has important implications for further research in this field which is heavily dependent on mouse models.

Further information

Please click here for more information about the work of Dr Emma Kidd

Please click here for more information about the work of Dr Rhian Thomas

Please click here for more information about the work of Professor Mark Good