Familial Alzheimer's disease (FAD) is a rare autosomal dominant form of Alzheimer's disease, generally affecting individuals below the age of 60, which results in offspring of affected parents having a 50% chance of developing the disease themselves. It was at UCL, in 1991, where the first FAD gene (APP) was found, and during the last two decades FAD research has accelerated significantly.
Longitudinal study of FAD
The Dementia Research Centre has been conducting a longitudinal study into familial Alzheimer's disease (FAD) for over twenty years. Individuals who come from families affected by FAD undergo annual neurological, imaging, and neuropsychological assessments. As these subjects are assessed prior to the onset of any symptoms, this provides invaluable information on the earliest signs of the disease. Also, by tracking individuals over long time periods, this gives us an insight into how the disease progresses. A key strength of the DRC is its expertise in developing new improved brain scanning techniques and sensitive cognitive tests, and this remains one of the main focuses of this study. It is hoped that this work will improve our ability to diagnose the disease earlier, as well as track disease progression and assess any impact new therapies might be having on the degenerative process. A large number of publications have already been produced as a result of this study.
Longitudinal (DIAN-L) study
In 2008 the Dominantly Inherited Alzheimer’s Network (DIAN) was established. DIAN is an international collaborative project, with 14 centres worldwide participating. The aim of DIAN is to study, on a larger scale than has ever been possible before, those changes that occur in the brain in FAD, even prior to the onset of any symptoms. The research visits involve a number of assessments, including neurological examination, psychology testing, an MRI scan, blood tests and an optional lumbar puncture. So far, the results of the DIAN observational study have been very enlightening, with several influential research papers published. The DRC is the only UK site involved in the DIAN study. Many individuals who participate in DIAN-L also participate in the DRC’s longitudinal study of FAD (see above).
Dominantly Inherited Alzheimer’s Disease Network treatment trial (DIAN-TU)
Year 2014 heralded an exciting new phase of FAD research – the first multicentre trial to assess the use potential disease modifying treatments in both symptomatic and presymptomatic FAD. We are currently the only DIAN-TU study site in the UK and have been recruiting participants since July 2014. The use of two different drugs (gantenerumab and solanezumab) are being assessed, with the hope being that at least one will be able to prevent, or slow, the progression of the disease.
Another, exciting line of investigation that the DRC is involved in involves collecting a small sample of skin from the arm of someone with an FAD gene mutation, and using these in a laboratory to make FAD nerve cells.