Scientists Discover Potential New Early Sign of Alzheimer's to Watch For

Early signs of Alzheimer's Disease
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One of the problems with diagnosing Alzheimer’s disease is that by the time the currently recognized signs and symptoms manifest, disease and damage to the brain has progressed significantly.

Early signs to watch for when suspecting that a loved one may be suffering from Alzheimer’s disease include:

• Memory loss
• Changes in ability to develop and follow a plan or work with numbers
• Difficulty in completing normal daily tasks
• Confusion with time or place
• Difficulty with understanding visual images and spatial relationships
• Difficulty with following or joining a conversation
• Misplacing things and losing the ability to retrace steps
• Poor judgment
• Withdrawal from work or social activities
• Mood and personality changes

In a recent study published in Science Translational Medicine, researchers believe that a disruption in normal sleeping patterns may be the newest and earliest sign of impeding Alzheimer’s disease.

Their hypothesis is based on a study of mice that are genetically designed to develop Alzheimer’s disease—evidenced as increased amyloid plaque formation in the brain—as they age. They discovered that when amyloid plaque formation begins on mouse brains, that the test animals normal sleep/wake cycles are disrupted.

Amyloid plaques consist primarily of accumulations of short fragments of beta amyloid protein that are normally present in the cerebrospinal fluid of a healthy individual. These bits of protein are eventually biochemically cleared out of the person’s system without causing harm. However, in the case of Alzheimer’s disease, for unknown reasons the bits of amyloid protein begin to accumulate into permanent plaques between nerve cells that eventually causes brain cell death and shrinkage of the brain. The first signs of amyloid plaque formation shows up as difficulties with thinking, learning, memory and planning.

Previous studies have shown that that the brain levels of a primary ingredient of plaques fluctuates in a predictable pattern-- when young mice are awake, their levels increase; when the mice go to sleep, their levels decrease. However, when the mice are artificially prevented from having a normal sleep/wake cycle, the levels of the primary ingredient of plaque do not decrease, but remains high and plaques form.

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More recently, the researchers found that the levels of the beta amyloid protein fragments fluctuate in the cerebrospinal fluid in both men and mice when healthy and not showing signs of Alzheimer’s disease. However, when the first sign of Alzheimer's disease manifests and plaque formation is in progress, the levels of beta amyloid stop fluctuating.

“We suspect that the plaques are pulling in amyloid beta, removing it from the processes that would normally clear it from the brain,” says senior author David M. Holtzman, MD, head of Washington University’s Department of Neurology.

Furthermore, the mice began to experience disruptions of their normal sleep/wake cycles with their sleep time dropping from an average of 40 minutes per hour to 30 minutes per hour.

To determine whether the amyloid beta protein are linked to the sleep changes in the affected mice, a vaccine against the amyloid beta protein was given to a young group of Alzheimer’s disease model mice before they reached the age when disease would begin. What the researchers found was that as the vaccinated mice aged, they did not develop brain plaques as they normally would, their beta amyloid proteins continued to fluctuate as normal, and their sleeping patterns did not change.

The significance of this is that if humans follow the same symptoms of sleep disruption correlated with beta amyloid protein changes and plaque formation, then sleep disruption could be the earliest sign of impeding Alzheimer’s disease and offer a way to test the effectiveness of anti-Alzheimer’s drugs and treatment.

“If sleep abnormalities begin this early in the course of human Alzheimer’s disease, those changes could provide us with an easily detectable sign of pathology,” says Dr. Holtzman. “As we start to treat Alzheimer’s patients before the onset of dementia, the presence or absence of sleep problems may be a rapid indicator of whether the new treatments are succeeding.”

Currently, research is ongoing to determine whether and what type of sleep disruption may occur in humans who are beginning to develop Alzheimer’s disease.

Image Source: Courtesy of MorgueFile

Reference: “Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of β-Amyloid in Mice with Alzheimer’s Disease Pathology” Science Translational Medicine (5 September 2012) Vol. 4, Issue 150, p. 150; Jee Hoon Roh, et al.

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