Tying together the toxic proteins in Alzheimer’s Disease

This week the Basic Science domain in the Centre for Dementia Prevention was involved with an important new publication looking into two key proteins that are involved with the development of dementia. In this new paper, the Spires-Jones lab asked the question of whether Amyloid Beta and Tau are working together to cause the build up of toxic proteins or to damage the brain cells and connections between them.

Image

Alzheimer’s disease is the most common cause of dementia in older people. During the course of Alzheimer’s disease two hallmark proteins build up in the brain. These are Amyloid Beta, which aggregates into plaques, and Tau which aggregates into structures called tangles. These two proteins are thought to cause the brain degeneration that leads to dementia symptoms, but importantly, we do not know yet how these two toxic players interact in damaging the brain. Amyloid plaques accumulate early in the disease process, starting long before symptoms appear, and Tau tangles accumulate and spread through the brain later in the disease, and more closely parallel the damage to brain cells and dementia symptoms.  One of the key questions in the field is how do early changes in amyloid lead to later changes in tau that appear to be more important in causing brain degeneration?

To see whether Amyloid Beta and Tau are working together to cause the build up of toxic proteins the authors developed a new model that expresses human versions of Amyloid Beta and Tau to see how these two proteins interact. They found that extra Tau increases the size of Amyloid Beta plaques, and increases some of the damage to cells around plaques. However, combining the two proteins in this model did not cause more loss of brain cells or the synaptic connections between them. First author Rosemary Jackson (pictured) emphasises that this finding is important because it increases our knowledge of how these two very important proteins interact to cause Alzheimer’s Disease. This study also raises new questions that are currently being worked on in the lab such as does lowering levels of Tau protect the brain from the damaging effects of Amyloid Beta?  We will be certain to give more background and explain our future papers looking into these questions on the road to a better understanding of the brain changes underlying dementia and how we can prevent or reverse these changes.

Jackson, R. J., Rudinskiy, N., Herrmann, A. G., Croft, S., Kim, J. M., Petrova, V., Ramos-Rodriguez, J. J., Pitstick, R., Wegmann, S., Garcia-Alloza, M., Carlson, G. A., Hyman, B. T. and Spires-Jones, T. L. (2016), Human tau increases amyloid β plaque size but not amyloid β-mediated synapse loss in a novel mouse model of Alzheimer’s disease. Eur J Neurosci