Alzheimer's disease affects about 4 million Americans and 6 million in the European Union. The commonest form is sporadic late-onset Alzheimer's disease which affects those over the age of 65 years and which is different from the much rarer early-onset familial Alzheimer's disease that is genetically determined.
Sporadic late-onset Alzheimer's disease is a multifactorial and polygenic disease in which several genetic and non-genetic risk factors have to be present to trigger the disease.
In 1993 scientists at Duke University, North Carolina discovered the first susceptibility gene for late-onset Alzheimer's disease, the E4 variant of the apolipoprotein E gene on chromosome 19. People with this genetic variant have about a 4-fold increased risk of developing Alzheimer's disease compared with people without the gene, but many people carry the E4 variant without developing Alzheimer's disease.
The OPTIMA (Oxford Project to Investigate Memory and Ageing) team, headed by Professor David Smith, has now discovered that the gene for butyrylcholinesterase (a protein that is present in the amyloid plaques and neurofibrillary tangles in the brain in Alzheimer's disease) on chromosome 3 interacts with the apolipoprotein E gene greatly to increase the risk of developing Alzheimer's disease.
People over 65 years old who carry the K variant of the gene for butyrylcholinesterase as well as the E4 variant of apolipoprotein E have a 30-fold increased risk of developing Alzheimer's disease compared with people who carry neither genetic variant. About 6% of the Caucasian population carry both variants while more than half the population carries neither variant.
These findings need to be replicated in other centres but, if confirmed, they will help to increase our understanding of how the Alzheimer¹s disease is triggered and they will also have implications for identifying elderly people at risk of the disease.
OPTIMA is a longitudinal clinico-pathological study that has been supported by Bristol-Myers Squibb Co. since 1988. It is based in the Department of Pharmacology and Radcliffe Infirmary, Oxford, UK.
Reference: Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease. D.J. Lehmann, C. Johnston & A.D. Smith, Human Molecular Genetics Vol. 6, No. 11, 1933-1936.
For further information please contact: Professor A. David Smith, University Department of Pharmacology, Mansfield Rd. Oxford OX1 3QT. Tel: 01865-271883; FAX: 01865-271882
Journal
Human Molecular Genetics