Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Popular Alzheimer's theory may be false trail

17.06.2009
The idea that anti-inflammatory drugs might protect people struggling with dementia from Alzheimer's disease has received a blow with the online release of a study of human brain tissue in Acta Neuropathologica.

Researchers with the McKnight Brain Institute of the University of Florida, in collaboration with scientists at the University of Frankfurt, Germany, discovered that inflammation of microglia -- an abundant cell type that plays an important supporting role in the brain -- does not appear to be associated with dementia in Alzheimer's disease.

The finding supports recent clinical trial results that indicate anti-inflammatory drugs are not effective at fighting dementia in patients with Alzheimer's disease, which affects about 5.3 million Americans.

"For almost 20 years now, it's been claimed that brain inflammation contributes to the development of Alzheimer's disease dementia, and based on that claim, numerous clinical trials with anti-inflammatory drugs have been conducted. They have been unsuccessful," said Wolfgang Streit, a professor of neuroscience at the College of Medicine. "In the current paper we have shown that the brain's immune system, made up of microglia, is not activated in the brains of Alzheimer's patients, as would be the case if there were inflammation. Instead, microglia are degenerating. We claim that a loss of microglial cells contributes to the loss of neurons, and thus to the development of dementia."

Microglial cells are a subset of a very large population of brain cells known as glial cells. Neurons are the workhorse cells of the brain, enabling thought and movement, but glia are their faithful sidekicks, providing physical and nutritional support.

Glial cells, which outnumber neurons 10-to-1, are at the heart of a popular explanation for Alzheimer's disease that suggests protein fragments called beta amyloid -- Abeta for short -- clump together in the spaces between brain cells, causing memory loss and dementia. Inflammation theories suggest that microglia become "activated" and mount an immune response to these protein clumps, and instead of being helpful, a toxic release of chemicals occurs, worsening the disease effects.

However, Streit's high-resolution observations did not find evidence that Abeta activates, or inflames, human microglia cells. Nor did researchers find evidence that inflammation is to blame for brain cell death.

"This paper potentially represents a paradigm shift in the way we look at Alzheimer's disease," said Mark A. Smith, a professor of pathology at Case Western Reserve University and editor-in-chief of the Journal of Alzheimer's Disease. "The study goes against the very popular idea of neuro-inflammation; instead, the idea that microglia are senescent is consistent with a number of features of the disease.

"The research makes a very good case that these cells are subject to aging," said Smith, who did not participate in the study. "These cells were thought to be activated (against Alzheimer's), but this paper makes a strong case that they are not. The study has taken a novel approach that has led to a novel insight."

Using a commercially available antibody, Streit for the first time created a marker for microglial cells in human brain specimens that had been in chemical storage. The specimens were from 19 people with varying degrees of Alzheimer's, ranging from severe to none at all. Two of the samples were from Down syndrome patients, who are known to develop Alzheimer's pathology in middle age.

When researchers examined these cells alongside neurons under a high-resolution microscope, they found that -- unless an infection had occurred elsewhere in the body -- microglial cells from Alzheimer's patients were not distinctly larger or unusually shaped, which would have been the case had they been inflamed.

"What I expected to see is activated microglia right next to dying neurons," Streit said. "That is what I did not find. What I propose is glia are dying, and the neurons lose support. We now need to find out what caused glia to degenerate. Rather than trying to find ways to inhibit microglia with anti-inflammatory drugs, we need to find ways to keep them alive and strong. It's a whole new field."

The microglial cells had a tangled, fragmented appearance, similar to neurons in the throes of Alzheimer's disease or -- old age.

"These cells are breaking into pieces," said Streit, who collaborated with Alzheimer's researcher Dr. Heiko Braak, of the Institute for Clinical Neuroanatomy in Frankfurt. "They are on their way out. For the first time, we are proving that microglial cells are subject to aging and may undergo degeneration, and that the loss of these cells precedes the loss of neurons. Research has been so focused on finding activated microglia, no one considered that these cells were degenerating and neurons lost support."

The work was supported by the National Institutes of Health, the German Research Council and the Evelyn F. and William L. McKnight Brain Institute.

Alzheimer's disease is the sixth leading cause of death in the United States and the fifth leading cause of death for Americans 65 and older, according to the Alzheimer's Association. The association estimates Alzheimer's and other dementias cost Medicare, Medicaid and businesses a total of $148 billion annually.

April Frawley Birdwell | EurekAlert!
Further information:
http://www.ufl.edu

More articles from Health and Medicine:

nachricht Improving memory with magnets
28.03.2017 | McGill University

nachricht Graphene-based neural probes probe brain activity in high resolution
28.03.2017 | Graphene Flagship

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>