Discovery Of Two New Alzheimer’s Genes

An international team of scientists led by the University of Cardiff in Wales, UK have discovered two new genes responsible for significantly increasing the risk of Alzheimer’s disease.

80 percent of the risks of Alzheimer’s are due to genetic factors. Until this study only one gene, APOE4 had been linked to Alzheimer’s disease increasing the probability of risk by two to four times. But it only accounts for a very small part of the genetic risk. There was therefore extensive world wide research for other disease related genes which till date remained elusive. Hence the significance of the discovery of the two new genes CLU and PICALM linked to the disease.

Hailed by Welsh Minister Rhodri Morgan as a “real feather in the cap of Welsh science”, the study is a collaborative effort of 80 researchers from the UK, Ireland, France, Germany, Belgium, Greece and the US, The result was published in the online issue of Nature Genetics on 6 September.

The extensive nature of the study adds further significance to it.

DNA samples from more than 19,000 older European and US residents. 7,000 of the donors had Alzheimer’s, while the others had no clinical symptoms of the disease. The samples came from brain and blood tissue made available and analyzed by dozens of laboratories in the UK, Ireland, Germany, Belgium, Greece and the US. By looking at more than 600,000 common DNA markers, the investigators found the two new genes were linked to higher risk of Alzheimer’s; they also confirmed the importance of APOE4.

The CLU gene codes for a protein called clusterin which normally protects the brain in several ways. Any variation in structure of CLU negates the protective effect of clusterin paving the way to Alzheimer’s   and the build up of amyloid protein plaques around brain cells.  This is supported by the research of Dr John C. Morris, of Washington University in St Louis, Missouri, US which shows   that   in mice the CLU gene may be involved in the formation of amyloid deposits in the brain.

Changes in genes which affect synapses are likely to have a direct effect on disease development. PICALM affects synapses responsible for forming memories and other brain functions.

Dr Alison M. Goate, a professor of neurology at Washington University who identified the first mutation in APP gene on chromosome 21 considers that the two genes are significant though their effect seems to be smaller than that of APOE. 19 to 20% risk by APOE, while it is only 10% by the two new genes.

The researchers also found 13 other genes which when investigated further for possible links with Alzheimer’s risk may yield more useful discoveries. A French-led team has in fact identified a third gene CRL, their paper appearing in the same issue of Nature Genetics.

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