University of Bristol
Functional deficits in a novel murine model of frontotemporal lobar degeneration
Alzheimer's Research UK
Frontotemporal dementia (FTD) is the second most common cause of dementia in people below 65. Genetic analysis of families with inherited FTD has revealed that mutations in 7 different genes can result in FTD. Each of these genes encodes for production of a specific protein and the disease-causing mutations cause these proteins to become dysfunctional. By investigating how FTD-causing mutations disturb the function of proteins we will better understand how FTD and related diseases arise. Here we aim to understand how mutations in the CHMP2B gene disturb brain function and thus cause FTD. The UCL group has genetically engineered mice to possess a mutated form of the human CHMP2B gene. This results in age-dependent development of brain pathology reminiscent of FTD. This award funds a link with Bristol scientists who specialise in measuring activity of brain circuits. Using electrical and optical real-time measurements the teams will collaborate to analyse how parts of the brain important in memory and other important functions become disturbed in these disease model mice. This will provide new information about why the brain works poorly in FTD sufferers, and may also shed light on why neurones die in this and related disease such as Alzheimers.