Alzheimer's, Parkinson's decoded
Scientists at the
University of Virginia School of Medicine have identified a potential
explanation for the mysterious death of specific brain cells seen in
Alzheimer's, Parkinson's and other neurodegenerative diseases.
According
to the new research, the cells may die because of naturally occurring
gene variation in brain cells that were, until recently, assumed to be
genetically identical.
The variation, called
‘somatic mosaicism,’ could explain why neurons in the temporal lobe are
the first to die in Alzheimer's, for example and why dopaminergic
neurons are the first to die in Parkinson's.
Speaking about it,
neuroscientist Michael McConnell said, “This has been a big open
question in neuroscience, particularly in various neurodegenerative
diseases,” adding, "What is this selective vulnerability? What underlies
it? And so now, with our work, the hypotheses moving forward are that
it could be that different regions of the brain actually have a
different garden of these [variations] in young individuals and that
sets up different regions for decline later in life."
The findings of the
unexpected variation in the genetic makeup of individual brain cells
emerged from McConnell's investigations into schizophrenia. That
discovery may help explain not just schizophrenia but depression,
bipolar disorder, autism and other conditions.
McConnell expected that
this mosaicism would increase with age that mutations would accumulate
over time. What he and his collaborators at Johns Hopkins found is
exactly the opposite – younger people had the most mosaicism and older
people had the least.
Based on the finding,
McConnell believes that the neurons with significant genetic variation,
known as CNV neurons, may be the most vulnerable to dying. And that
could explain the idiosyncratic death of specific neurons in different
neurodegenerative diseases. People with the most CNV neurons in the
temporal lobe, for example, might be likely to develop Alzheimer's.
"Because I'm collaborating with the Lieber Institute and they have this
fantastic brain bank, now I can look at individuals' frontal cortex [for
the schizophrenia research] and I can look at the temporal lobe in
those same individuals," McConnell said.