Cellular mechanisms leading to Alzheimer’s disease

What are the aims of this group?

Despite extensive research, the fundamental cellular mechanisms leading to the development of Alzheimer’s disease are poorly understood. As a result treatment of this condition is inadequate, with current medications only being around 30% effective in delaying or relieving the symptoms of Alzheimer’s disease. Prof Conway’s group targets the key areas of Alzheimer’s disease research that remain unanswered such as understanding the underlying pathogenic mechanisms that govern protein misfolding in the brain and identifying new and novel indicators in the blood that can help to diagnose Alzheimer’s disease.

What have they found out so far?

One of their most recent studies aimed to understand how a mechanism responsible for removing unfolded proteins in the brain malfunctions, resulting in the build-up of protein aggregates. Such aggregates are commonly seen in neurodegenerative conditions such as Alzheimer’s disease.

They previously reported that the level of hBCAT proteins is significantly higher in the brains of patients with Alzheimer’s disease when compared to those of a similar age without any type of dementia. Using their current model system, this group have shown that an increased hBCAT level in brain cells reduces vesicle formation, a process necessary for optimal clearance of protein aggregates. This leads to an abnormal build-up of protein aggregates, and so may be one of the pathways leading to the degeneration of brain cells in Alzheimer’s disease.

What are they doing next?

The metabolic pathways governed by hBCAT are controlled and regulated through metabolites in the blood. This work is therefore being extended to understand how external influences can be manipulated to regulate protein misfolding in the brain.

Aligned to these projects are biomarker studies, where in collaboration with Dr Liz Coulthard and Prof Risto Kauppinen they aim to identify signature profiles to differentiate between patients with mild cognitive impairment that will or will not progress to develop Alzheimer’s disease. Biomarkers are biological properties that can be detected and measured in parts of the body, such as the blood, and are a much needed tool in this area to help with quickly and accurately diagnosing Alzheimer’s disease and dementia.

Why is this important?

Together, understanding of these pathways will identify possible therapeutic targets and new biomarkers, which will provide the foundation to develop new strategies for the prevention, treatment and diagnosis of Alzheimer’s disease and related conditions.

Further information

Please click here for more information about the work of Professor Myra Conway.