The newly identified rare mutation in the TM2D3 gene was about 10 times more common in people on the remote Nordic island country in the North Atlantic Ocean compared to the European population in general.
But scientists said the variant remains quite rare and was present in fewer than one per cent of the Icelandic population.
And the prevalence of Alzheimer’s disease in Iceland is comparable to that seen elsewhere in the world,
The variant in the TM2D3 gene was linked to increased risk and earlier onset of Alzheimer’s disease.
Alzheimer’s disease is the most common form of dementia, affecting about three in ten adults aged over 85
While scientists have already identified many common genetic variants that contribute to the disease, rare mutations with significant effects in the population have been more difficult to discover, except in rather isolated families.
To find such rare variations, a collaboration of Alzheimer’s researchers throughout the US and Europe performed an analysis covering more than 11,000 genes in 1,393 late-onset Alzheimer’s disease patients.
They identified a variant in the TM2D3 gene.
Johanna Jakobsdottir of the Icelandic Heart Association and Sven van der Lee of Erasmus University in Rotterdam also performed experiments in a fruit fly model, in which human TM2D3 was substituted for an equivalent fly gene.
This demonstrated that the discovered variant interferes with the Notch signaling pathway.
Other Notch signaling factors have previously been shown to participate in the generation of amyloid plaque brain pathology in Alzheimer’s disease.
M2D3 gene has not previously been linked to Alzheimer’s, and may have importance for understanding the mechanisms that contribute to the late-onset form of the disease.
Ms Jakobsdottir said: “We have found a rare variant in the TM2D3 gene that correlates with risk of late-onset Alzheimer’s disease and showed that it likely interferes with the Notch signaling pathway, which has relevance for Alzheimer’s disease as other Notch signaling factors play a role in amyloid plaque pathology.
“However, we have not proven causality and further study is needed, including additional experiments in the fly, DNA sequencing to identify additional variants, and RNA sequencing to study effects on gene expression.”
The study was published in PLOS Genetics.
Source : EXPRESS