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Molecule discovered that may prevent development of Alzheimer’s disease

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According to the Los Angeles County Department of Public Health, Alzheimer’s disease is the seventh most common cause of death in the county. Before death occurs, sufferers of the disease are progressively stripped of their ability to function. A team of researchers from Harvard Medical School (Boston, Massachusetts) and Rush University Medical Center (Chicago, Illinois) have discovered that individuals who develop early cognitive decline appear to have lower levels of a stress-protecting protein in their brains. The finding might lead to early diagnosis and therapies that can prevent the development of Alzheimer's disease and other forms of dementia. The findings were published March 19 in the journal Nature.

The study authors note that the nerve cells in the human brain must function over an entire lifetime; however, the mechanisms that preserve their function and protect against degeneration during ageing are unknown. They note that induction of the repressor element 1-silencing transcription factor (REST) is a universal feature of normal ageing in two areas of the human brain: the cortex and the hippocampus. However, with mild cognitive impairment and Alzheimer’s disease, REST is lost.

The investigators measured levels of the REST protein in the brains of individuals after their death. Before they died, the individuals had undergone tests of cognitive function. The researchers found that those with higher cognitive function at the time of their death had three times more REST in their prefrontal cortex, which is the outer portion of the front part of the brain involved in a number of cognitive functions including planning and personality.

Biochemical analysis has found that REST represses genes that promote cell death and the manifestations of Alzheimer’s disease; in addition, the molecule induces the expression of stress response genes. In addition, REST may protect neurons from oxidative stress and amyloid β-protein toxicity. They note that removal of REST fromn the mouse brain results in age-related neurodegeneration.

During normal ageing, REST; however, in Alzheimer’s disease and other forms of dementias, REST is lost from the nuclei of neurons. The researchers note that REST levels during ageing closely correlate with cognitive preservation and longevity. Thus, maintaining REST levels in the brain may prevent cognitive decline in the ageing brain.