July 13, 2017
Researchers
led by Arizona State University (ASU) and the Translational Genomics Research
Institute (TGen) have identified altered expression of a gene called ANK1,
which only recently has been associated with memory robbing Alzheimer's
disease, in specific cells in the brain.
Using an extremely precise method of isolating cells called
"laser capture microdissection," researchers looked at three specific cell types -
microglia, astrocytes and neurons - in the brain tissue of individuals with a
pathological diagnosis of Alzheimer's disease, and compared them to brain
samples from healthy individuals and those with Parkinson's disease.
Following sequencing of each of these cell types, the ASU-TGen led
team found that altered ANK1 expression originates in microglia, a type of
immune cell found in the brain and central nervous system, according to the
study published today in the scientific journal PLOS ONE.
"Although previous genetic and epigenetic-wide association
studies had shown a significant association between ANK1 and AD, they were
unable to identify the class of cells that may be responsible for such
association because of the use of brain homogenates. Here, we provide evidence
that microglia are the source of the previously observed differential
expression patterns in the ANK1 gene in Alzheimer's disease," said Dr.
Diego Mastroeni, an Assistant Research Professor at Biodesign's ASU-Banner
Neurodegenerative Disease Research Center, and the study's lead author.
All three of the cell types in this study were derived from the
hippocampus, a small looping structure shaped like a seahorse (its name derives
from the Greek words for horse and sea monster). The hippocampus resides
deep inside the human brain and plays important roles in the consolidation of
both short-term and long-term memory, and in the spatial memory that enables
the body to navigate.
In Alzheimer's disease - and other forms of dementia - the
hippocampus is one of the first regions of the brain to suffer damage,
resulting in short-term memory loss and disorientation. Individuals with
extensive damage to the hippocampus are unable to form and retain new memories.
"Using our unique data set, we show that in the hippocampus,
ANK1 is significantly increased four-fold in Alzheimer's disease microglia, but
not in neurons or astrocytes from the same individuals," said Dr. Winnie
Liang, an Assistant Professor, Director of TGen Scientific Operations and
Director of TGen's Collaborative Sequencing Center, and one of the study's
authors. "These findings emphasize that expression analysis of defined
classes of cells is required to understand what genes and pathways are
dysregulated in Alzheimer's."
Alzheimer's
features many signs of chronic inflammation, and microglia are key regulators
of the inflammatory cascade, proposed as an early event in the development of
Alzheimer's, the study said.
Because the study
found that ANK1 also was increased two-fold in Parkinson's disease, "these
data suggest that alterations in ANK1, at lease in microglia, may not be
disease specific, but rather a response, or phenotype associated with
neurodegeneration … more specifically, neuroinflammation."
More than 5
million Americans have Alzheimer's, an irreversible and progressive brain disorder that slowly
destroys memory, thinking skills and eventually the ability to conduct even the
simplest of tasks. For most patients, symptoms first appear in the mid-60s. For
older Americans, it is the third leading cause of death, following heart
disease and cancer, according to the National Institutes of Health.
"The success
of this, and many other studies, owes a great deal to the support and
collaborative nature of the people of the Arizona Alzheimer's Consortium.
The results obtained in this work emphasize the importance of methods that
enable us to characterize the molecular profile of defined cells, either as a group
or as single cells, that have been defined by any of several means," said
Dr. Paul Coleman, Research Professor at Biodesign's ASU-Banner
Neurodegenerative Disease Research Center, and the study's senior author.
Dr. Eric Reiman,
Director of the Arizona Alzheimer's Consortium and Clinical Director of
Neurogenomics at TGen, said: "This study demonstrates the value of
bringing together talented researchers from different disciplines and
organizations to advance the scientific fight against Alzheimer's disease."
Journal reference: PLoS ONE
Provided by: Translational
Genomics Research Institute
https://medicalxpress.com/news/2017-07-source-cell-specific-alzheimer-disease.html
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