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Alzheimer's Signs Found in Brains of Young Adults With Gene Mutation
Date:11/6/2012

TUESDAY, Nov. 6 (HealthDay News) -- Scientists have discovered the earliest known evidence of Alzheimer's disease in people with a gene mutation that causes a rare form of the disease that begins at a young age.

The findings from the two studies could improve understanding of how and why Alzheimer's progresses and possibly lead to earlier detection of the disease and improved treatments, according to the researchers.

In one study, researchers conducted brain scans and other tests on 44 young adults, aged 18 to 26, in Colombia. Twenty of them had a mutation of a gene called presenilin 1 (PSEN1) that causes Alzheimer's to develop at an unusually early age, and 24 did not have the mutation. None of the participants showed any signs of mental decline at the time of the study.

There were notable differences in brain structure and function between the young adults with the PSEN1 mutation and those without it. The participants with the PSEN1 mutation had greater activity in regions of the brain called the hippocampus and the parahippocampus, and less gray matter in certain brain areas.

In addition, the cerebrospinal fluid of the young adults with the PSEN1 mutation had higher levels of amyloid beta protein, which is a component of the amyloid plaques in the brain that are associated with Alzheimer's disease.

On average, people with the PSEN1 mutation start to show signs of mental decline at age 45. This study shows that biomarkers in these people are evident at least 20 years before symptoms begin to appear. That's earlier than any previous study has found.

The study was published Nov. 5 in The Lancet Neurology.

"These findings suggest that brain changes begin many years before the clinical onset of Alzheimer's disease, and even before the onset of amyloid plaque deposition. They raise new questions about the earliest brain changes involved in the predisposition to Alzheimer's and the extent to which they could be targeted by future prevention therapies," study leader Dr. Eric Reiman, at the Banner Alzheimer's Institute, in Arizona, said in a journal news release.

In a second study, the same group of researchers found that amyloid plaques begin to accumulate in the brains of people with the PSEN1 mutation when they are in their late 20s.

The findings will "help set the stage for the evaluation of treatments to prevent familial Alzheimer's disease, and hopefully aid our understanding of the early stages of late-onset Alzheimer's disease, which is more widespread," the researchers wrote in the report.

Nick Fox, a professor at the Institute of Neurology at University College London, wrote a journal commentary that accompanied the first study.

"These findings question our models of Alzheimer's disease on several fronts. They suggest that neurodegenerative changes occur over 20 years before symptom onset and somewhat earlier than was suggested by previous brain imaging studies of individuals at risk of inherited Alzheimer's disease," Fox wrote.

"Further research is needed, but one interpretation of these results might be that they add to the accumulating evidence that Alzheimer's disease is characterized by a long presymptomatic period of slowly progressive changes that can potentially be tracked, thereby opening up a therapeutic window for early intervention," he added.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more about Alzheimer's disease.

-- Robert Preidt

SOURCE: The Lancet Neurology, news release, Nov. 5, 2012


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