Everything we do, say or think is the result of electrical signals that pass through nerve cells in the brain. These nerve cells form vast networks that break down in diseases like Alzheimer’s, causing symptoms like memory loss and confusion. In these networks, brain cells connect to one another at points called synapses. Changes at these synapses may impact the functioning of nerve cell networks in Alzheimer’s, but it’s not clear how or when this happens, or if it could be repaired. In this Fellowship, Dr Witton is uncovering more about this relationship, relating these changes to patterns of electrical activity in the brain in diseases like Alzheimer’s.
A better understanding of these changes will lay important groundwork for using tests of this activity to monitor Alzheimer’s in people. Dr Witton is also identifying points in the disease process where future treatment hopes have the greatest chance of succeeding.
The tau protein is a hallmark of a number of diseases that cause dementia, including frontotemporal dementia and Alzheimer’s. The build-up of tau in nerve cells in the brain is strongly linked to changes in both synapses and nerve cell networks. The precise relationship between these factors is an area of interest for dementia researchers – uncovering how changes in synaptic activity affect the function of nerve cell networks will help to inform the development of treatments that can stop these changes from taking place.
While the techniques Dr Witton is using can provide accurate pictures of changes taking place in the brain in mice, this approach isn’t possible in living people. However, measuring electrical signals in the human brain is relatively simple and non-invasive, using a process called electroencephalography (EEG). As such, Dr Witton’s work could lay the foundations for an EEG test that could be used to monitor the progression of diseases like Alzheimer’s in people.
Dr Witton is using a state-of-the-art microscope, along with electrical recording techniques, to study how the breakdown of synapses affects nerve cell networks in mice that have the hallmark dementia protein tau. This work is uncovering what typical electrical activity looks like at specific points along the disease progression. Dr Witton is constructing a timeline of these events, improving understanding of the key processes that are involved. By carefully characterising how this build-up of tau damages communication between nerve cells, the team is improving understanding how diseases like Alzheimer’s progress.
As part of this Fellowship, Dr Witton is also stopping the build-up of tau in mice at different points along the course of the disease. Information gained from this is hugely important for identifying windows of opportunity where treatment approaches targeting tau could be most effective.
Dr Jonathan Witton
University of Bristol
1 January 2016 - 31 December 2018
Full project name
Dysfunctional synaptic and neuronal network encoding in tauopathy-associated dementia