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The Role of Grey Matter in Alzheimer's Disease

By Monica-GomezApril 20, 2015

Learn more from Monica Gomez and her article about recent research into the role of grey matter in Alzheimer’s disease.

Research Reveals the Role of Grey Matter in Alzheimer’s

As Americans live longer, we are encountering a significant increase in the senior population who suffer from neurodegenerative conditions, including Alzheimer’s. The Alzheimer’s Association points out that experts believe Alzheimer’s is the result of various factors, including age and genetics, which are identified as major risk factors. Yet, many questions about the disease still remain open.

Two recent medical studies offer critical information about additional factors that may impact the development and treatment of Alzheimer’s. Scientists in the UK found that a specific network within grey matter was more vulnerable to age-related neurodegeneration, and that it degenerated sooner than other brain areas. Stateside, researchers discovered that a protein created under heat shock could improve a dysfunctional actin cytoskeleton, which is linked to neurodegenerative disorders.

Medical News Today first reported that scientists at the Oxford University Functional MRI of the Brain Centre, led by Dr. Gwenaelle Douaud, applied a theory called “retrogenesis” from the 1880s to current research on grey matter. Grey matter is the cortex of the brain, which is responsible for muscle control, memory, emotions, speech, decision-making, self-control and sensory perception. The “retrogenesis” theory of brain change suggests that brain ability declines in reverse order to how it develops.

Following this line of inquiry, the scientists relied on Magnetic Resonance Imaging (MRI) scans of 484 people aged 8-85 to look for age-related patterns. Their analysis revealed two important findings:

  1. A particular network within the grey matter links most of the higher order functions of the brain.
  2. This network develops later than the rest of the brain and is the first to show signs of degeneration with age.

Moreover, when the researchers compared the scans of healthy individuals with those of people who suffer from Alzheimer’s and schizophrenia, they found that this particular brain network might play a crucial role in these different diseases. It seems like this area of the brain is more vulnerable to both Alzheimer’s and schizophrenia.

This study further reconciles two hypotheses that have previously been discussed entirely separately in scientific literature, according to Dr. Douaud:

  • The brain damage caused by schizophrenia and Alzheimer’s are related to higher order parts of the brain
  • These parts of the brain are not as developed in other primates, which also don’t develop schizophrenia or Alzheimer’s, implying that these diseases are a result of human evolution and longer lifespans

According to Professor Perry, chairman of the Medical Research Council’s Neurosciences and Mental Health Board, which funded the research, there was no evidence that the same parts of the brain might be linked to such different diseases. Although doctors called schizophrenia “premature dementia” in the past.

“This large-scale and detailed study provides an important, and previously missing, link between development, aging, and disease processes in the brain. It raises important issues about possible genetic and environmental factors that may occur in early life and then have lifelong consequences,” Perry says.

Alzheimer’s and the HSF-1 Protein

While the findings from Oxford University research may provide us with new insights about the factors that contribute to Alzheimer’s, the discoveries made in a recent study from University of California, Berkeley, and University of Michigan could possibly lead to future treatments of this incurable disease.

The study was spearheaded by Andrew Dillin, who serves as the Thomas and Stacey Siebel Distinguished Chair of Stem Cell Research in the Department of Molecular and Cell Biology and the Howard Hughes Medical Institute investigator at the University of California, Berkeley.

Science Daily reports that a team of researchers challenges a long held scientific belief about how the brain reacts to misfolded proteins during heat shock. For over 30 years, scientists believed that cells exposed to heat, such as a fever, produced a protein called heat shock factor-1 (HSF-1), which would launch “chaperone” molecules to refold misfolded proteins. An accumulation of misfolded proteins has been associated with neurodegenerative diseases. Hence, scientists believed that artificially increasing HSF-1 would reduce misfolded proteins and thus protect the brain. Yet, this process had the unintended consequences of increasing cancer risk.

In the past, scientists believed that HSF-1 was simply responsible for releasing chaperone cells. However, Dillin and his team found in experiments that the protein plays a much bigger part:

  1. HSF-1 also stabilizes the cell’s cytoskeleton, which transports necessary supplies — including healing chaperones — throughout the cell.
  2. HSF-1 regulates a gene called pat-10, which produces a protein that stabilizes actin, a building block of the cytoskeleton.

As a result, Dillin and his colleagues’ research suggests that instead of increasing HSF-1 to release chaperone molecules, the protein ought to be used for strengthening the cytoskeleton in order to protect against neurodegenerative diseases. This alternative approach might also avoid the cancerous side effects of boosting HSF-1. Furthermore, Dillin and his team even suspect that the protein’s main function is actually reinforcing the cytoskeleton, rather than triggering the release of chaperones. They mutated HSF-1 so that it would no longer boost chaperones, showing that it was not essential to surviving heat stress as long as the cytoskeleton was stable.

Even though further experiments are needed to rule out errors, the University of California, Berkeley and the University of Michigan research teams hope that their findings will pave the way for novel treatments of neurodegenerative diseases.

As researchers learn more about how the brain develops and works at all ages, they are discovering links that they previously thought were unrelated. Further research into these connections may open new avenues for future preventative treatments.

Did you know about the research into the connection between grey matter and Alzheimer’s? What did you find most interesting about the results? Share your thoughts with us in the comments below.

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