Broken `circadian clock` linked to Alzheimer`s disease

Washington: Researchers have shown that brain cell damage similar to that seen in Alzheimer's disease and other disorders results when a gene that controls the sleep-wake cycle and other bodily rhythms is disabled.

A new discovery, by Scientists at Washington University School of Medicine in St. Louis and the University of Pennsylvaniam may help explain the surprisingly strong connections between sleep problems and neurodegenerative conditions such as Alzheimer's disease.

The researchers found evidence that disabling a circadian clock gene that controls the daily rhythms of many bodily processes blocks a part of the brain's housekeeping cycle that neutralizes dangerous chemicals known as free radicals.

"Normally in the hours leading up to midday, the brain increases its production of certain antioxidant enzymes, which help clean up free radicals. When clock genes are disabled, though, this surge no longer occurs, and the free radicals may linger in the brain and cause more damage," first author Erik Musiek, assistant professor of neurology at the School of Medicine, said.

Musiek studied mice lacking a master clock gene called Bmal1. Without this gene, activities that normally occur at particular times of day are disrupted.

In the new study, Musiek found that as the mice aged, many of their brain cells became damaged and did not function normally. The patterns of damage were similar to those seen in Alzheimer's disease and other neurodegenerative disorders.

This led Musiek to examine the production of key antioxidant enzymes, which usually neutralize and help clear free radicals from the brain, thereby limiting damage. He found levels of several antioxidant proteins peak in the middle of the day in healthy mice. However, this surge is absent in mice lacking Bmal1. Without the surge, free radicals may remain in the brain longer, contributing to the damage Musiek observed.

The study was published in the journal of Clinical Investigation.

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