The Contribution of Mitochondrial Dysfunction to Alzheimer's disease

Alzheimer's Disease (AD) likely manifests through a combination of genetic inheritance and environmental factors. Currently, the biggest risk factor for developing AD is age. Neurons are terminally differentiated and must be maintained throughout our entire lifetimes.

However, during ageing levels of oxidative stress, in the form of reactive oxygen species (ROS) accumulate, which leads to oxidation of proteins/lipids, induces DNA damage and may eventually trigger neurodegeneration. Mitochondria are also compromised and produce less ATP.

Antioxidant mechanisms which usually protect neurons are decreased with age, and decreased to an even greater extent in the AD patient brain.

We have recently found that the AD risk gene WWOX is key regulator of metabolism, redox and mitochondrial health and that metabolism shifts are associated with amyloid beta (AB) protein aggregation and anticipate that other risk gene will be involved in metabolic regulation. Dysregulation of the metabolism and redox is largely understudied in the context of age-dependent neurodegeneration.

The focus of this PhD studentship is to determine the mechanism of how redox and metabolism changes manifest in a number of AD models