Understanding how protein changes lead to reduced brain blood flow and increased dementia risk

Scientific title: Angioneurins VEGF & BDNF and their influence on hypoperfusion in dementia

Type of project: PhD Studentship, co-supervised by Professor Seth Love

What do we already know?

There is a substantial overlap between Alzheimer’s disease (AD) and vascular dementia (VaD).  A reduction in blood flow (known as hypoperfusion) is present in most AD patients and has also been shown to be a predictor of AD in asymptomatic patients with a family history of the dementia.

Vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) are angioneurins: proteins that influence both neuronal and vascular cell functions including neuroprotection, the regulation of angiogenesis (appropriate growth and maintenance of blood vessels) and synaptic plasticity (forming new memories).  These proteins are therefore important in supporting proper brain function by maintaining appropriate blood flow to the brain, however the expression and functions of these proteins are altered in AD.

What is this research trying to find out?

VEGF and BDNF are known to interact, and this project aims to characterise these interactions in order to work out how they change in neurodegenerative diseases such as AD, VaD and dementia with Lewy bodies (DLB).  They hypothesise that the alterations in the expression and interactions of VEGF, BDNF, and their receptors contribute to hypoperfusion and neurodegeneration.

How will they do this?

Levels of VEGF, BEDF, and their receptors will be measured in post-mortem brain samples from healthy individuals and individuals diagnosed with AD and DLB.  The researchers will then use living neuronal cell lines – applying amyloid-β, ischaemic conditions or AD-associated mutations – to understand how the signalling pathways involved in the VEGF and BDNF interactions are altered in AD.   A range of biochemical techniques will be used for this, including cell culture, ELISA, western blotting, immunocytochemistry and qPCR.  The results from these experiments will aid interpretation of the VEGF and BDNF measurements from human post-mortem tissue.

Why is it important?

By understanding the underlying roles of VEGF and BDNF and the effect of their interaction in the initiation and progression of dementia, we may be able to develop better drugs to treat dementia.  For example, VEGF- or BDNF-related drugs to maintain cerebral perfusion, reducing ischaemic damage and promoting amyloid-β removal.

Further information

Please click here for more information about the work of Dr Shelley Allen-Birt