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Cortex area thinner in youth with Alzheimer's-related gene

A part of the brain first affected by Alzheimers disease is thinner in youth with a risk gene for the disorder, a brain imaging study by researchers at the National Institute of Mental Health (NIMH), one of the National Institutes of Health (NIH), has found. A thinner entorhinal cortex, a structure in the lower middle part of the brains outer mantle, may render these youth more susceptible to degenerative changes and mental decline later in life, propose Drs. Philip Shaw, Judith Rapoport, Jay Giedd, and NIMH and McGill University colleagues. They report on how variation in the gene for apoliproprotein (ApoE), which plays a critical role in repair of brain cells, affects development of this learning and memory hub in the June, 2007 Lancet Neurology.

"People with the Alzheimers-related variant of the ApoE gene might not be able to sustain much aging-related tissue loss in the entorhinal cortex before they cross a critical threshold," explained Shaw. "But the early thinning appears to be a harmless genetic variation rather than a disease-related change, as it did not affect youths intellectual ability. Only long-term brain imaging studies of healthy aging adults will confirm whether this anatomical signature detectible in childhood predisposes for Alzheimers."

It was already known that adults destined to develop Alzheimers disease tend to have a smaller and less active entorhinal cortex. This structure is the first to shrink in volume and to develop the neurofibrillary tangles characteristic of the disorder.

Previous studies had also implicated in Alzheimers one of three versions of a gene that produces ApoE. The ApoE4 variant occurs in 10-25 percent of the general population, but in 40 percent of late-onset Alzheimers patients. The strongest genetic risk factor for the disease discovered to date, ApoE4 has been linked to altered brain activity in adults and impaired neuronal development.

Shaw and colleagues s
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
23-Apr-2007


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