Protein glycation in Alzheimer’s disease: implications for dementia diagnosis, prognosis and therapy

There are currently no disease markers that can be used as indicators for Alzheimer’s disease (AD) or for other non-AD dementias. Novel disease markers highlighting these aspects of the disease are urgently needed to improve the accuracy of AD disease diagnosis, prognosis, and therapies. Age-related modifications of proteins, such as glycation, have been implicated in the pathology of AD but have been largely overlooked as potential biomarkers. We have developed a new technology using fluorescent boronic acid-based ligands to detect glycated proteins and have identified a number of novel modified proteins in post-mortem brain that would support a role for the immune system in the pathology of AD. Our proposal aims to 1) extend these post-mortem human studies to include additional forms and stages of dementia (with Brains for Dementia Research, London), 2) assess the potential use of identified markers in blood and saliva samples from dementia patients and 3) use glycated migration factors discovered in our pilot analyses, for detailed investigations into the hitherto unexplored molecular links between impaired glucose handling, immunity, inflammation and dementia.