March 2015 Research Update

March 2015 Research Update

With extensive funding from the Alzheimer’s Research UK (ARUK), 3 successive programme grants plus multiple additional awards totalling over £2.5M, I have established ongoing collaborations with an additional 10 ARUK Network Centres which has resulted in the Nottingham ARUK DNA Bank. Currently this holds 5500+ samples from Alzheimer’s patients and controls. Our collaboration with Professor Steven Younkin at the Mayo Clinic, Jacksonville, USA provides access to an additional 6000 samples making our combined resource of well over 10000 samples one of the largest collections worldwide and an extremely valuable and unique resource. Our continuing collaboration ensures that the University of Nottingham remains at the forefront of research into Alzheimer’s disease (AD) genetics. Many papers have been published on the top 25 AD genes. In the post genome-wide association study (GWAS) era we are in an ideal position to exploit emerging data and have embarked on a series of targeted and whole exome next generation sequencing projects with over £1.5M funding.

Until very recently the e4 allele of the APOE gene was the only universally accepted risk factor for late-onset Alzheimer’s disease (LOAD). This was despite intensive worldwide effort to detect additional genetic components of LOAD. With the advent of the GWAS results for LOAD (September 2009, April 2011 and December 2013), 21 new genes have recently been identified. Samples (n=2200) from the ARUK DNA Bank were integral to these studies. The Nottingham ART collection of samples played a significant role in the success of these projects.

These results have resulted in the AD field taking a quantum leap forward; 21 new genes is a hugely significant contribution to our understanding of this devastating disease. When this news first broke it was covered by all the major news agencies and for a while was the top news story worldwide; it also received extensive TV coverage. Time magazine selected it in the top ten medical breakthroughs of 2009. With the discovery of these additional genes we now can explain a significant proportion of the genetic component in AD. I represent the UK on IGAP (International Genetics of Alzheimer’s Project) which is a worldwide consortium collaborating on all aspects of the genetics of AD.

Another area of our work, some aspects of which are covered by patents, relates to the development of a diagnostic device for early detection of AD potentially decades before the first clinical symptoms are seen thereby identifying individuals who are most likely to benefit from early therapeutic intervention. This AD biomarker programme was initially funded by ARUK and led to a Medical Research Council Developmental Pathway Funding Scheme award.

March 30, 2015