The Centre for Dementia Prevention Basic Science domain studies the early development of neurodegenerative disease. In a new publication Eleanor Pickett (pictured below) and colleagues looked at a protein called tau and the role of tau tangles in the very earliest stages of Alzheimer’s disease development on a mouse model. The authors highlight the importance of boosting the natural immune system to prevent the disease development.
Alzheimer’s disease is the most common cause of dementia and is characterised by progressive memory loss. Memory is made possible by the ability of synapses – tiny connections between brain cells that adapt to environmental inputs to the brain. In Alzheimer’s disease these connections are lost, which means the brain cells can no longer communicate with each other effectively and this is believed to underpin the symptoms of dementia.
Two proteins, called amyloid-beta and tau, have been implicated in the loss of these synapses. As the disease progresses, these proteins change and build up in the brain to form structures termed amyloid-beta plaques and tau tangles – the two hallmarks of Alzheimer’s disease.
Abnormal tau protein initially begins to clump together into tangles in areas of the brain that are important for memory. These tangles then spread throughout the brain as symptoms progress. How this protein spreads has yet to be determined, however one potential route is via the breakdown of synapses, which release tau towards the next cell. To test whether the collapse of synapses is necessary for tau to advance throughout the brain, the authors of the paper developed a mouse model that mimics the spread of this protein. It was found that abnormal tau spreads between brain cells before synapses are lost. The findings suggest that the spread of tau begins very early in the disease process before synapses break down and therefore supports the evolving therapeutic approach of trying to prevent the spread of tau by using immunotherapies and focusing research efforts on the prevention of the disease progressing into symptomatic dementia.
Pickett E.K, Henstridge C.M, Allison E, Pitstick, R., Pooler, A., Wegmann, S., Carlson, G., Hyman, B.T., Spires-Jones, T.L. (2017). Spread of tau down neural circuits precedes synapse and neuronal loss in the rTgTauEC mouse model of early Alzheimer’s disease. Synapse.