“Goddess of fate” gene shows Alzheimer’s potential

By | Health & Wellness
New research has shown that a variant of a gene associated with longevity also causes improved brain function in it's carriers, providing clues to treat conditions such as Alzheimer's. Credit image@ Patric Hagmann et al., wikimedia commons

Getting older and cognitive function go hand in hand: our brain’s capacity to absorb knowledge and create new ideas, develops over time. Indeed, the majority of calories (up to 60 per cent) used during gestation goes to developing brain tissue, which has allowed humans to become the dominant, in a certain sense, species on the planet.

However, this cognitive function begins to fade as one matures. Indeed, recent research suggests that the reason our brain seems to “slow down” in our elderly years, is actually due to the fact that the organ itself has absorbed so much data over time it requires a while to sort it out into a cohesive thought!

That being said, ageing and cognitive decline are also forming a pattern in modern and economically developed societies, with conditions like Alzheimer’s emerging more and more. However, some individuals contain within their genome anti-ageing factors that could, certainly in theory, help reverse this trend.

New research has unravelled the secrets behind a gene associated with longevity, and has shown that it leads to some significant cognitive effects.

Indeed, the allele, or variant, of the KLOTHO gene, which is associated with a long lifespan, has also caused enhanced brain function, reports a study funded by the National Institutes of Health.

The paper was published in the scientific journal Cell, and is available to view online as an open access article.  

The KLOTHO sequence codes for proteins are generally attributed to a range of organs, ranging from the intestine and the prostate to even the placenta. However, a version of these compounds is also found circulating freely in the bloodstream.

Named after the mythological Greek goddess of fate Klotho, research has shown that individuals who possess one variant of the KLOTHO gene, KL-VS, tend to live longer.

In this study, the scientists found that those who possessed the above variant also showed improved scores during cognitive ability tests.

Interestingly, and perhaps importantly, these effects were seen in subjects regardless of age, sex or the presence of genes like apolipoprotein 4 gene, which is associated with and increased prevalence of Alzheimer’s in individuals that carry it.

The researchers firstly examined whether the KL-VS genetic variant of KLOTHO could anticipate healthy brain ageing in humans. To do this the study included a total of 718 individuals, ranging from 52 to 85 years of age, all of whom showed healthy brain function.

Of this study sample, twenty six per cent of the individuals tested heterozygous for the KL-VS variant, that is to say they possessed one copy of the allele (had they had two copies, they would be called homozygous for the gene).

Following the completion of the cognitive tests, these individual scored higher than those who were void of the gene.

Thus, the KLOTHO proteins produced by this variant have a beneficial effect on the cognitive abilities of its host, which means that this could be a particularly promising research avenue, said Roderick Corriveau, Ph.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), speaking to the National Institute of Health news release of the study.

“Although preliminary, they suggest that a form of KLOTHO could be used to enhance cognition” an important tool for people diagnosed with dementia, he added.

To test this hypothesis, the team looked to overproduce the KLOTHO protein in mice test subjects, via genetically enhancement.

The results of these test showed that mice that overproduced the protein lived longer and scored better in cognitive ability tests, much like the human study concluded. Blood tests revealed that the KLOTHO protein was indeed abundant in the bloodstream as well as the hippocampus, a region of the brain associated with certain types of learning.

In order to learn something new, the process is thought to develop the communication between synapses, the junction between two nerve cells, in the brain. In the hippocampus, the synapses use a compound known as glutamate, controlled by GluN2B subunits. The researchers showed that klotho-enhanced mice developed more of these subunits, thus strengthening the connection between the two nerves, boosting learning and intelligence.

Importantly, the researchers also found this compound age-independent.

“If we could boost the brain’s ability to function,” said Dr. Dena Dubal, an assistant professor of neurology and lead author of the paper, “we may be able to counter dementias”, which would make the outlook on such conditions very promising indeed.

What other research would you like to see conducted in field of Alzheimers and other related conditions?


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