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Alzheimer's and heart attacks share the same genes

10.12.2010
'Test ready' according to new study based on controversial statistical techniques

Alzheimer and heart attacks have been found to share common genetic basis. The research leads the way to the first genetic test on developing the risk of the diseases even at a young age. According to Federico Licastro, an immunologist at the University of Bologna who coordinated the study published in the scientific journal, Journal of Alzheimer's Disease, a test is now ready.

"They are already selling it in America", he says, citing the case of a private firm in New Mexico (USA) that collaborated on the study. "But the tests could easily be also conducted wherever, using a simple blood test".

It comes as no surprise that the prospect of personalised tests is also very attractive to healthcare companies. Alzheimer and heart attacks are two relatively common diseases, Alzheimer being the most frequent form of senile dementia: by 85, it affects one in five women and one in ten men. Heart attacks, along with other cardiovascular problems, are one of the most widespread diseases and one of the main causes of death, affecting approximately 12.5 per cent of the population.

Very little was known to date about the connection between the two diseases. However, some epidemiological data appeared to suggest such a link. For example, coronary problems had already been associated with elevated frequency of Alzheimer, just as other issues such as hypertension, high cholesterol, diabetes and other typical cardiovascular risk factors. Some genes, controlling for inflammatory processes and cholesterol metabolism, were also known to be connected in some way to both Alzheimer and heart attacks.

What the researchers did was to examine the DNA of 1800 people (280 of whom had suffered a heart attack, 257 Alzheimer and 1307 healthy subjects, used as a control group), in their search for genetic factors suggesting a risk common to the two diseases. Their research proved positive; indeed there is some overlapping between the congenital risks of being affected by Alzheimer and suffering a heart attack. This common genetic predisposition was found in 30 percent of heart attack sufferers and 40 per cent of those affected by Alzheimer. To reach this conclusion, the researches separated all those tested into six groups, with varying levels of risk; low for groups one, two and three; groups two and three only being classified as low risk under the age of 65. Groups four, five and six were classified as high; group five only having a high risk of suffering a heart attack (over the age of 55). Groups four and six, on the other hand, were the two main groups that the researchers focused on. Both had a high risk of suffering a heart attack (under the age of 40 in group four and between the ages of 40 and 54 in group six) as well as Alzheimer (under the age of 65 in group four and over it, in group six). Indeed, it was these last two groups that showed a common genetic predisposition.

"Until now, we only knew about individual genes linked to both diseases and this was not sufficient to develop an individual test for the risk", explained Licastro. "However, we have now been able to identify a genetic profile of several genes partially common to both diseases. This is the leap in quality that now enables us to conduct a test and assess a profile partially specific to both diseases".

Based on the result of the test, the researchers say that you can, for example, decide whether or not to monitor the situation by regular medical checks and more in-depth medical exams. Furthermore, the link between the two diseases tells us a bit more about their origin. According to Licastro, "the core of the genetic risk profile consists of genes that are involved in synthesizing and transporting cholesterol and in controlling for inflammation, which, therefore, appears to be at the root of both diseases". This means that not only can you conduct tests to identify the diseases, you can also define appropriate life-styles to prevent heart and circulation problems and Alzheimer.

However, the researchers understand that technical ingredient that brought about the success of the test is likely to be controversial. Indeed, to study the DNA of their patients, they had to resort to an innovative statistical technique called grade of membership analysis. Although this approach is already applied to the study of other problems, from melanomas to schizophrenia, it is still being debated within the international scientific community. "However, it is only by using such statistical analyses", says Licastro, "that such diseases can be tested, conducting tests on only a few hundred cases. Classical statistics would require us to test 10, 12 or even 20 or 30 thousand cases".

In short, the debate is still open. Professor Federico Licastro and his group, which includes the very young Elisa Porcellini and Ilaria Carbone, will continue looking into the question in more depth, hoping to find new genetic links between the two diseases. Critics may contest the statistical results or even put forward counter tests based on classical statistics. For now, however, what everyone seems to agree on is that a healthy life-style that helps keep cholesterol and hypertension under control is not only beneficial to the heart but also to the brain.

Luigi Valeri | EurekAlert!
Further information:
http://www.unibo.it

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