Genes
help cognition withstand damage in brain from Alzheimer’s, Parkinson’s:
“The pathologies
(damage) in the brain that stroke, Alzheimer’s disease and other neurological
conditions cause in older adults only partially explain the memory loss,
reduced reasoning ability and other cognitive impairments that result from
these conditions. Little is known about why the effects of brain pathology vary
among people who develop it.
“Now researchers have
discovered two genes, known as UNC5C and ENC1, that are associated with aging
individuals having better memory and brain function than would be expected,
given the amount of pathologies that accumulated in their brains. They reported
their findings in an article published today [April 25, 2017] in the journal PLOS Medicine.
“‘Most of the cognitive
loss that we experience in older age remains unexplained. Certain individuals
are very resistant to the pathologies of the aging brain, while others may be
particularly vulnerable,’ says study senior investigator David Bennett, MD, who directs the Rush Alzheimer’s Disease Center.
“These potentially
damaging pathologies include the buildup of harmful proteins known as amyloid
plaques and neurofibrillary tangles that occur in Alzheimer’s disease; the protein deposits known
as Lewy bodies that accompany Parkinson’s disease and Lewy body dementia; and
the death of massive amounts of brain cells caused by stroke.
“Identifying genes that
contribute to resistance to these and other brain pathologies could provide
researchers with new targets for developing medications that would enhance the
brains of aging adults to resist Alzheimer’s disease and other neurological
conditions, Bennett says.
Study used genetic analysis of 979 organ donors’
brain tissue:
“The researchers drew
on a vast trove of data, including genetic analyses, generated by two ongoing
long-term studies of aging based at Rush University Medical Center, which
includes study participants’ donation of their brains for research after their
death. These participants were tested annually to measure their cognitive
function, allowing for a comparison of the decrease in cognitive function with
the development of any pathology found when their brains were autopsied after
their deaths.
“Using this information
for 979 participants, the researchers assessed how much each person’s thinking
ability withstood the development of memory loss despite the accumulation of
brain pathology – in other words, how resilient they were to pathology. Then
they conducted a complex, multiple step analysis ‘to identify segments of the
human genome (i.e, genes) that help us to maintain cognitive function in the
face of advancing age and disease,’ explains study senior investigator Philip
De Jager, MD, PhD, professor of neurology at Columbia University Medical
Center.
“The innovative
approach combined an analysis of the human genome – the complete set of genes
in a person — with an evaluation of the epigenome — changes to DNA that helps
determine which genes can be ‘read’ so its protein is made. Epigenome in part
reflects how our brain responds to life experiences and exposures to
environmental factors.
“The analysis
identified UNC5C and ENC1 as being associated with cognitive resilience. In
addition, the researchers found that TMEM106B — a gene whose presence
previously had been identified as possibly protecting against age-related
frontotemporal lobar degeneration — also may play a role in brain resilience.
“‘These genes should be
studied further to expand our understanding of molecular mechanisms relevant to
cognitive resilience that could be translated into prognostic and therapeutic
tools for dementia prevention,’ the researchers write in the paper’s summary.
“The PLOS Medicine article presenting the
study’s findings is titled ‘Identification of genes associated with
dissociation of cognitive performance and neuropathological burden: Multistep
analysis of genetic, epigenetic, and transcriptional data.’ The study included
researchers at Rush University Medical Center, the Broad Institute, Brigham and
Women’s Hospital/Harvard Medical School, Columbia University Medical Center,
The Illinois Institute of Technology, the T.H. Chan School of Public Health and
the University of British Columbia.
“The work was supported
by grants from the National Institute on Aging. The investigators are indebted
to the study participants.”
This article is from Rush University Medical Center, Chicago, Illinois
"Memory loss is not inevitable as you age. Research at Rush suggests that the following lifestyle changes have the potential to slow mental decline and delay symptoms associated with Alzheimer’s:
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