Scientists have found a genetic variation thought to delay the start of Alzheimer’s disease, based on a study of 71 descendants of the same ancestral family from northern Columbia who have passed down a rare and severe form of Alzheimer’s disease. Members of this extended family carry a mutation in a gene called PSEN1 (Paisa Mutation) which can cause the development of the disease earlier than usual.
The study was carried out by researchers from the Australian National University, The University of Antioquia in Columbia, University Medical Centre Hamburg-Eppendorf, New York University, Nathan Kline Institute for Psychiatric Research, the University of Kentucky and Flinders University. The research conducted was a genetic study where researchers selected a group of people who were affected by a rare form of Alzheimer’s disease. Research involved genetic analysis and statistical tests to see whether other genetic changes could explain why some family members got Alzheimer’s disease earlier than others.
The research involved selecting 71 people from this family group to see if they carried a mutation in a gene called PSEN1 (sometimes known as the Paisa mutation). The average age for developing Alzheimer’s, for people carrying this mutation is 49, although other people developed Alzheimer’s much later. Researchers also analysed the DNA of 128 people who did not have the Paisa mutation and developed Alzheimer’s disease later in life.
Researchers identified several genetic variations which related to the onset of Alzheimer’s disease. They were most interested in variations of the apolipoprotein E (APOE) gene. This gene is responsible for making a protein that combines with fats to help repair damage in the brain. One form of this gene (known as allele) APOE*E4 is known to be associated with an increased risk of Alzheimer’s disease in older people. There is evidence that the presence of one genetic variation, the APOE*E2 allele in the DNA of people carrjying the Paisa mutation seemed to delay the start of Alzheimer’s disease by around 12 years (95% confidence interval 8.07 to 15.41 years).
When the researchers interpreted these results they said “We have defined major mutations modifying Alzheimer’s disease age of onset in members of a multigenerational extended family carrying the (Paisa) mutation. One of the modifier genes reported herein was also associated with the (age of onset) in sporadic cases from the general population.”
Written by Claire Collier