Hereditary Alzheimer's disease is caused by mutations in one of three genes. Carriers of the gene are 50 percent likely to pass the defect on to each of their children. Hereditary Alzheimer's disease is extremely rare (less than 1% of all Alzheimer's disease cases) - but those who carry it inevitably suffer from dementia, usually even before the age of 60.
The Dominantly Inherited Alzheimer Network (DIAN), established in 2008 in the U.S., has the purpose of facilitating and promoting research into genetically caused forms of Alzheimer's disease (https://dian.wustl.edu/). The rare genetic forms of Alzheimer's result from mutations in one of three genes (APP, PSEN1 or PSEN2). In the first phase of the DIAN study, affected persons will be identified, and their preclinical changes will be studied. The aim of DIAN is for findings relative to patients' changes to lead to a better understanding of the pathobiological cascade that, in carriers of a relevant mutation, can lead to Alzheimer's. It is also hoped that such findings can improve our understanding of sporadic Alzheimer's disease, which is very common. Plans call for a future second phase that will include therapy studies.
The DIAN study is a longitudinal multicentric study. Participants in the study, of whom there are already more than 400, are examined at two-year intervals. The group of participants includes persons whose biological parents (father or mother) or siblings have one of the three gene mutations APP, PSEN1 or PSEN2. Alzheimer's sufferers can be suspected of having an autosomal, dominantly inherited form of Alzheimer's if they were not older than 60 at the onset of the disease, and if other members of their family have also developed the disease at an age of 60 or younger. To be eligible for the study, persons need to be unaware of their mutation status. Whether or not they are already showing symptoms is not important. The minimum age for participants is 18.
The examinations in the framework of the study will include a detailed physical examination and an interview, both conducted by a study investigator. They will also include a detailed neuropsychological testing (with testing of memory functions and other aspects of cognitive performance), the taking of a blood sample for testing that will include genetic testing, a lumbar puncture (collection of cerebrospinal fluid), a cranial MRI scan and a cranial positron emission tomography scan (FDG PET/MRI and PiB PET/MRI).