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The Making of Medicine

An Explanation for Brain Cell Death in Alzheimer’s, Parkinson’s

Now we may know why specific brain cells die in Alzheimer’s, Parkinson’s and other neurodegenerative diseases.

Our Mike McConnell, who has been conducting fascinating research into schizophrenia, has determined that his research could have great relevance for conditions such as Alzheimer’s. As part of his studies of schizophrenia, Dr. McConnell discovered unexpected genetic variation in individual brain cells — cells that had been assumed to be genetically identical.

Probing into this further, Dr. McConnell assumed that this genetic variation — known as “somatic mosaicism” — would increase with age. Mutations, he reasoned, would build up over time. But what he found was quite the opposite: Older people had much less mosaicism than younger people. He called it “a perfect anti-correlation with age.”

Based on that, Dr. McConnell believes that neurons with significant genetic variation, known as CNV neurons, may be at the greatest risk of death. That could explain the idiosyncratic loss of specific neurons in various neurodegenerative diseases. For example, folks with the most CNV neurons in the temporal lobe could be primed to develop Alzheimer’s.

Dr. McConnell, of the Center for Brain Immunology and Glia (BIG), plans to conduct further investigation to better understand what is happening. So far, he has only looked at neurons in the frontal cortex, and he plans to start looking at neurons from both the frontal cortex and the temporal lobe in the brains of the same individuals. “Now I can really start to map things out more carefully,” he said, “building an atlas of different brain regions from many individuals.”

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