New Alzheimer’s genes

An international research team led by the Alzheimer Center and the Human Genetics
Department of Amsterdam UMC has discovered two new ‘Alzheimer genes’.
Colleagues Henne Holstege and Marc Hulsman have made a significant contribution
to this research.

Evidence has also been provided for another new gene. A hereditary damage to one of
these genes can lead to a significantly increased risk of Alzheimer’s disease. The study is published in Nature Genetics.

The study compared more than 32,000 genomes from Alzheimer’s disease patients and healthy individuals. The researchers looked for rare harmful genetic mutations with an
increased risk of Alzheimer’s disease. They found that deleterious mutations in the genes ATP8B4 and ABCA 1 can lead to an increased risk of Alzheimer’s disease. This has not been observed before. In addition, the researchers discovered that deleterious mutations in the ADAM10 gene probably also lead to an increased risk of Alzheimer’s disease. However, additional confirmatory research is needed for this gene. Together with ADAM10, there are now nine genes of which it is known that hereditary damage to the gene can lead to an
increased risk of Alzheimer’s.

Insight

All genes found are involved in maintaining brain health. For example, the two newly discovered Alzheimer’s genes are involved in the processing of the Alzheimer’s protein amyloid and in the function of the brain’s immune system. The finding that precisely these genes are more often disrupted in Alzheimer’s patients provides more insight into the processes that go wrong in the brains of people with Alzheimer’s disease.

Susceptibility to Alzheimer’s

The younger the Alzheimer’s patient, the greater the genetic nature of the disease: it is estimated that more than 90% of the risk of Alzheimer’s disease in people under the age of 65 is due to hereditary factors, while the risk of Alzheimer’s disease around age 75 for about 60-80% can be explained by hereditary factors. However, with the genes that have now been found, the risk-increasing hereditary damage can only be determined in a minority of these ‘young’ Alzheimer’s patients. That is why the researchers are now comparing much larger groups of Alzheimer’s patients with healthy individuals so that they can identify more new genes that are involved in a higher susceptibility to developing Alzheimer’s. This is slowly but surely revealing which genes influence susceptibility to Alzheimer’s.

Start on time

With these new developments, it will become increasingly possible to estimate the degree of susceptibility and the nature of the susceptibility to this disease per person, long before symptoms manifest themselves. In the future, personalized treatment can then be started in time, before damage occurs in the brain. Studies of genes and proteins that are most affected in patients with Alzheimer’s disease are also important for the development of
personalized preventive treatments.

The study was carried out with French researchers from Pasteur Institute, Lille, and the University of Rouen. Read the full publication on these newly discovered Alzheimer’s genes in Nature Genetics.

Article: ontdekte alzheimergenen in Nature Genetics