He was the first to discover a mutation in the amyloid gene encoding the amyloid precursor protein (APP) which plays a key role in neurodegeneration associated with Alzheimer’s disease.
His research interests are in the genetic analysis of disease. Historically, he has worked on the genetic analysis of Alzheimer's disease and other dementias and more recently, on Parkinson's disease and other movement disorders and on motor neuron disease.
His early studies were on Mendelian forms of disease and these studies continue, but an increasing focus has been on the genetic analysis of complex traits related to disease. Additionally, this latter analysis has created an increasing interest in population genetics because the risk variants for human traits are likely to be different in different racial groups. In all cases the intention is to develop an understanding of the underlying genetics of a disorder both in the understanding of disease mechanisms and to help in the search for treatments.
Among his honours and awards are the Peter Debje Prize, University of Limburg, Belgium, for Alzheimer’s Research in 1991. The IPSEN Prize for Research into Alzheimer's disease in 1992. The Potamkin Prize from the American Academy of Neurology, for Alzheimer’s Research in 1993. The Allied Signal Prize for Research into Aging and the MetLife Prize for Research into Alzheimer’s disease in 1995. The Kaul Prize for Research into Alzheimer’s disease in 2002 and the Anne Marie Oprecht International Prize for research in Parkinson’s disease in 2008. He is a member of the academy of Medical Sciences and of the Royal Society of London. He was awarded the Khalid Iqbal Award for Lifetime Achievement in 2010 and the IFRAD Prize for Alzheimer’s Research in 2011.