The immense suffering of a Colombian family could help scientists develop treatments to delay the symptoms of dementia. The huge family carries a gene that sees many fall victim to early-onset Alzheimer's disease. Now research has revealed other genes that determine just how long people get before the disease makes itself felt.
One of the Spanish Conquistadors who colonized what is now Colombia in the 16th century carried the presenilin-1 mutation, which triggers early-onset Alzheimer's disease. Despite this burden, the individual has more than 5,000 known descendants. Since this family has remained largely isolated, the population has become highly inbred and has many common genes while experiencing a similar environment. For genetic researchers exploring the most common form of dementia, the population represents an invaluable resource, one which has been studied intensively for decades.
This research has shown that, even for those with the presenilin-1 mutation, there is a wide variation to when Alzheimer's strikes. The median age of diagnosis is 49, but examples have been recorded from the early 30s to late-70s. The wider availability of genetic sequencing gave an international team the tools to explore the genetic variation in DNA collected from 1,181 members of the family, many of whom have since died of Alzheimer's.
The findings have been published in Molecular Psychiatry. They include the identification of nine alleles, or gene variations, that affect the timing of dementia, with some delaying onset while others hasten it. Senior author Dr. Mauricio Arcos-Burgos of the Australian National University told IFLScience these alleles play a much larger role than environmental effects.
“If you can work out how to decelerate the disease, then you can have a profound impact,” Arcos-Burgos said in a statement. “I think it will be more successful to delay the onset of the disease than to prevent it completely. Even if we delay the onset by on average one year, that will mean nine million fewer people have the disease in 2050.”
The most powerful of these alleles is APOE *E2, with a delaying effect of approximately 12 years. Arcos-Burgos told IFLScience that APOE *E2's mechanism is not yet known. However, he hopes the alteration it causes to protein structures can be identified, making it possible to produce medicines that provide similar protection for people at high risk.
Arcos-Burgos is not the only researcher to see the potential of the presenilin-1 family. The U.S. National Institute of Health plans to spend $170 million (£110 million) on testing new Alzheimer's treatments on the descendants of this single individual. By creating a model that allows predictions of when onset should occur, Arcos-Burgos and his co-authors have provided a firmer base for measuring the effectiveness of these interventions.
The causes of Alzheimer's may vary. Arcos-Burgos told IFLScience. “We cannot say [that treatments that work on presenilin-1 carriers] will prove generally applicable,” he said. However, at least one of the variants his team identified exists in the wider community and appears likely to have relevant effects.
