Dominique Campion and his research team at the Insert unit 1079 "Genetics of cancer and neuropsychiatric diseases" in Rouen showed that in the families of 5 of 14 patients suffering from the disease, mutations were detected on the gene SORL1.
This gene regulates the production of a peptide involved in Alzheimer's disease.
Precise genetic mutations have been seen to play a part in early-onset forms of Alzheimer's disease.
However, there is a sub-population of patients in whom there is no mutation of these genes. So how can these patients, in whom there are no pre-established mutations, be suffering from early-onset Alzheimer's?
To answer this question, the research team working under the leadership of Dominique Campion and Didier Hannequin, studied the genes from 130 families suffering from early-onset forms of Alzheimer's disease.
These families were identified by 23 French hospital teams within the framework of the "Alzheimer Plan". Of these families, 116 presented mutations on the already known genes. But in the 14 remaining families, there was no mutation at all observed on these genes.
A study of the genome of the 14 families using new whole DNA sequencing techniques showed evidence of mutations on a new SORL1 gene. The SORL1 gene is a coding gene for a protein involved in the production of the beta-amyloid peptide. This protein is known to affect the functioning of the brain cells (see insert).
Two of the identified mutations are responsible for an under-expression of SORL1, resulting in an increase in the production of the beta-amyloid peptide.
"The mutations observed on SORL1 seem to contribute to the development of early-onset Alzheimer's disease. However, we still need to identify more clearly the way in which these mutations are transmitted on the SORL1 gene within families," Dominique Campion said.
The study has been published in the review Molecular Psychiatry.