A recent two-stage meta-analysis study has found 11 new genes believed to be involved in the onset of AlzheimerÔÇÖs Disease. The International Genomics of AlzheimerÔÇÖs Project (IGAP) consisted of four research groups from 145 academic institutions in Europe and the US. Professor Julie Williams led the UK team based at the MRC Centre for Neuropsychiatric Genetics & Genomics at Cardiff University. The project is the first international collaboration of AlzheimerÔÇÖs geneticists and has resulted in the discovery of more genes than any other study to date.
In 2009, Professor Williams brought together the European AlzheimerÔÇÖs Disease Initiative (EADI) France, the AlzheimerÔÇÖs Disease Genetics Consortium (ADGC) Pennsylvania, the neurology subgroup of the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) Boston and her own team the Genetic and Environmental Risk in AlzheimerÔÇÖs Disease (GERAD) in the largest ever study of itÔÇÖs kind, which was published in last months issue of Nature Genetics.
IGAP used data from genome wide association studies (GWAS) carried out by the four groups, in a two-part meta-analysis. GWAS involve the analysis of variants of genes (alleles) in individuals presenting particular traits, such as AlzheimerÔÇÖs. Presently, the molecular mechanisms and functions underlying these identified alleles are unknown: the associations are purely observational and based on their prevalence in individuals with AlzheimerÔÇÖs. However, one of the most pertinent discoveries of the GWAS, is the confirmation of the involvement of the immune system in the disease onset. In addition to this, it is also believed that┬á changes beyond genetic factors can influence the likelihood of developing the disease.
The way genes are observed interacting with the environment can be affected by environmental factors such as vascular health, obesity and alcohol consumption, indicating that it is not certain that carriers of the associated genes will develop AlzheimerÔÇÖs. Some overlap in gene association has also been observed between AlzheimerÔÇÖs and other types of dementia such as Vascular and Fronto-Temporal indicating that the diseases may share common genetic influences.
A possible implication of these findings is that curiosity and precaution may steer people to wanting to know whether or not they are carriers of these genes. Individuals with relatives who have had or currently have the disease may wish to know the likelihood that they too will develop AlzheimerÔÇÖs. In an interview with gair rhydd, Dr Denise Harold, Research Associate at the MRC Centre and colleague of Professor Williams, explained: ÔÇ£WeÔÇÖre finding pieces of the puzzle at the moment; I think we need to build up a better picture, so that people have a better understanding. I donÔÇÖt think at this point that weÔÇÖre able to predict whether somebody is going to get AlzheimerÔÇÖs Disease or notÔÇØ.
Professor Williams explains that the next steps for IGAP are to seek out people who are showing AlzheimerÔÇÖs at an earlier onset. Dr Harold further added that the teamÔÇÖs hypothesis is that in these┬áindividuals, genetic factors are stronger than in those presenting later on. Most cases of AlzheimerÔÇÖs Disease occur in adultÔÇÖs aged 65 and over suggesting a subtle genetic effect, combined with life-long environmental exposure. However, 5% of AlzheimerÔÇÖs cases occur at an earlier stage, indicating that something stronger than environmental factors is bringing onset about sooner. The teams hope that by analysing the DNA of individuals with early onset AlzheimerÔÇÖs Disease, they will be able to identify at a molecular level what is bringing the development of the disease forward.
This development in AlzheimerÔÇÖs research comes only weeks after a turning point that revealed a┬áchemical as a potential cure for neurodegeneration in diseases such as AlzheimerÔÇÖs, ParkinsonÔÇÖs and HuntingtonÔÇÖs. The compound, developed by the MRC Toxicology Unit at the University of Leicester, led┬áby Professor Giovanna Mallucci, was tested in samples of mice with PrionÔÇÖs disease. It was observed to stop the shut down of protein production within brain cells, which leads to cell death. It is hoped that this compound will, in the future, be developed into a treatment that can be used in humans to halt the damage to brain tissue caused by neurodegenerative diseases, such as AlzheimerÔÇÖs.
Since 2008, NHS health boards across Wales┬áhave been joining the 1000 Lives Campaign, which aims to improve and deliver high quality healthcare throughout the country. One programme within this campaign is ÔÇÿImproving Dementia CareÔÇÖ, by meeting 5 targets: reduce time between onset of symptoms and diagnosis, improve general hospital care for people with dementia, reduce inappropriate use of anti-psychotic medications, improve carer support and improve quality of care in dementia inpatient units. Furthermore, the UK government has recently announced its plans to invest an estimated ┬ú66.3 million┬áin dementia research in 2014/15. Combined investment, improvement in healthcare and collaborative research projects, will soon bring hope to those currently suffering and those who in the future may develop one of these devastating illnesses.
Sophie Howells
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