Major breakthrough in understanding Alzheimer’s
An international research group, led by a Cardiff University neuroscientist, has established new genetic links to Alzheimer’s disease
Alzheimer’s disease is the most common form of dementia in the elderly. It is a devastating, terminal disease in which the symptoms become more severe and debilitating over time. It is incurable: no treatments to delay or halt progression are currently available, only those that relieve the symptoms.
It is likely that a combination of risk factors are responsible for Alzheimer’s, such as age (> 65 years) and diet. Genetic inheritance is one such possible risk factor, and researchers have made a great advance: for the first time in more than 15 years, new genetic links to Alzheimer’s have been established.
The Study
Certain genes were already known to be associated with Alzheimer’s disease, but a very large sample was required to confirm these links. So, the largest ever genomewide association study of the disease, involving 16,000 people, was undertaken by an international group of researchers, led by Professor Julie Williams, Professor of Neuropsychological Genetics at Cardiff University School of Medicine in South Wales. The research was funded by the Wellcome Trust, Medical Research Council, Alzheimer’s Research Trust and Welsh Assembly Government, and the results were published in Nature Genetics, one of the highest impact journals in any field. It took place at the Centre for Neuropsychiatric Genetics and Genomics at the University – which is aimed specifically at harnessing the genetics revolution for research in mental disorders.
The genes
One gene was previously known as a risk factor for late-onset Alzheimer’s: APOE4 (apolipoprotein E). But by looking for common variants of other genes – singlenucleotide polymorphisms (single-letter differences in the DNA) – the study also found two further genes related to lateonset Alzheimer’s – CLU and PICALM.
As Professor Williams explains, ‘Both CLU and PICALM highlight new pathways that lead to Alzheimer’s disease. CLU is a clusterin – a type of protein – which normally protects the brain in a variety of ways. Variation in this gene could remove this protection and contribute to Alzheimer’s development. ‘PICALM is important at synapses – connections between brain cells – and is involved in the transport of molecules into and inside of nerve cells, helping form memories and other brain functions. We know that the health of synapses is closely related to memory performance in Alzheimer’s disease, thus changes in genes which affect synapses are likely to have a direct effect on disease development.’
A valuable new lead
The findings of the study have important potential future outcomes. New pathways and drug targets can be determined, therefore impacting on the development of treatments and cures for the disease. This can play a significant part in the knowledge of the diagnosis and prevention of Alzheimer’s, which in turn could affect public health policy – we could be more certain of risk factors, allowing better risk profiles to be established so that authorities can issue informed advice on lifestyle changes to help prevent the development of the disease.
It also shows that other genes can be identified using this method, and the team is already planning a larger study, involving 60,000 people, which is on target to be achieved within the next year.
- Ends -
Source: Advances Wales, 62
Professor Julie Williams, Professor of Neuropsychological
Genetics, Cardiff University Institute of Medical Genetics,
University Hospital of Wales, Heath Park, Cardiff
CF14 4XN, UK
Tel +44 (0)29 2068 7075
Email williamsj@cf.ac.uk (External Contact)
Web www.cardiff.ac.uk (External Link)
