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Study Probes Circadian Rhythm Genes for Alzheimer’s Clues

A certain gene variant previously implicated in employees with a poor tolerance to shift work may also be tied to a greater risk for Alzheimer’s disease in the elderly, according to a new Finnish study.

The findings are published in the journal SLEEP.

Alzheimer’s disease is a brain disorder that destroys memory and thinking skills over time. Some of its risk factors include disruption of sleep and the circadian rhythm, issues which are also quite common among shift workers.

Tolerance to the negative effects of shift work varies between individuals and is known to be partially linked to intrinsic genetic factors.

The study, led by Professor Tiina Paunio at the University of Helsinki and the National Institute for Health and Welfare in Finland, showed that in addition to Alzheimer’s diagnosis, the melatonin receptor 1A (MTNR1A) gene variation is linked to brain lesions visible in postmortem brain tissues.

Furthermore, when the expression of the MTNR1A gene was reduced in the cell culture, beta-amyloid protein characteristic of Alzheimer’s disease started to accumulate.

In a previous study, the researchers found that the same gene variation that predisposes to shift work fatigue is associated with lower levels of the MTNR1A gene expression in the brain. This means that the previous findings are compatible with the new findings made in the epidemiological cohorts and cell cultures.

The circadian rhythm regulates the release of melatonin, which in turn supports the circadian rhythm through its receptors. The new findings support the idea that the circadian rhythm may play a role in the development of Alzheimer’s disease.

“The finding of a common risk gene for both job-related exhaustion in shift workers and Alzheimer’s disease doesn’t directly mean that shift work would predispose to Alzheimer’s disease,” said Dr. Sonja Sulkava from the National Institute for Health and Welfare.

“However, the combination of genetic predisposition and a lifestyle that disrupts the circadian rhythm can increase the risk of Alzheimer’s disease. Another possible interpretation is that the brain dysfunctions related to Alzheimer’s disease impair the tolerance to shift work decades before the onset of the clinical disease.”

Paunio said even though the findings show a molecule-level link between the tolerance to shift work and Alzheimer’s disease, the genetic variation still has a minimal effect on the individual level and can’t be used for risk assessment or prediction.

The study involved Alzheimer’s patients and healthy controls living in Eastern Finland. The link could be seen in elderly cohorts but not in the younger patient and control cohorts.

Source: University of Helsinki

 



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