Prof Steffen Scholpp - University of Exeter

Striking the right balance - WNT signalling in Alzheimer's disease.

See glossary at bottom of page for definition of underlined words.

Summary

A neuron in the brain is connected to hundreds of other neurons by as many as 10,000 connection points, known as synapses. These synapses serve as points of communication between the neurons. The capacity of the brain to form new synapses and prune others throughout our lifetime is the basis of learning and memory. These changes in neuronal connections are known as synaptic plasticity. 

What do we already know?

Cell signalling, where crucial signals are passed from cell to cell, governs the necessary activities of neurons and coordinates multiple cellular actions. One of these signals known as WNT - regulates many aspects of synapses during brain development and in the adult brain. WNT signals increase the number, the density, and the strength of many synapses.

Alzheimer’s disease (AD) is primarily due to the loss of synaptic connections between neurons in the brain. Synapse loss leads to deterioration in memory and cognitive ability. Molecularly, we know of two significant changes in the diseased brain. Firstly, WNT is strongly decreased in AD brains, and therefore synaptic stability is reduced. Secondly, β-amyloid - a small molecule essential for controlling appropriate synaptic pruning - accumulates in the brain tissue.

What is this project trying to find out?

In this project, Prof Steffen Scholpp and his research team will test how WNT and β-amyloid interact in neurons. The researchers hypothesise that WNT signalling regulates the maintenance and growth of synaptic connections. In contrast, β-amyloid is required for pruning of unnecessary synapses. The research team will image the formation and disassembly of synaptic connections to test if WNT and β-amyloid keep a delicate balance between synaptic plasticity and synaptic stability - a step towards an understanding of the underlying molecular mechanism in AD.

Glossary

Gene – A gene is a region of DNA responsible for production of a protein.
Expression (of genes) – Expression of a gene involves the ‘turning on’ of the production of the relevant protein.
DNA Sequence – The precise ordering of the bases from which DNA is composed.
Epigenetic changes – Changes in the production of a protein that DO NOT involve changes in the DNA sequence.
Autopsy examination – an examination of a body after death to determine the cause of death or the character and extent of changes produced by disease.
Control Group – A control group in a scientific experiment is a group separated from the rest of the experiment, where the independent variable being tested cannot influence the results. In this case, the control group involves using brain tissue of people that did not have Alzheimers disease.

Further information

Please click here to find out more about dementia research at Exeter

Please click here for more information about the work of Adam Smith.

Please click here for more information about the work of Dr Katie Lunnon.

Please click here for more information about the work of Professor Jonathan Mill.

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