Navigation Links
Researchers close in on origins of main ingredient of Alzheimer's plaques
Date:4/9/2008

St. Louis, Aprl 8, 2008 The ability of brain cells to take in substances from their surface is essential to the production of a key ingredient in Alzheimer's brain plaques, neuroscientists at Washington University School of Medicine in St. Louis have learned.

The researchers used a drug to shut down the intake process, known as endocytosis, in a mouse model of Alzheimer's disease. The change led to a 70 percent drop in levels of amyloid beta, the protein fragment that clumps together to form Alzheimer's plaques. Importantly, they also found that endocytosis' ability to increase amyloid beta was coupled to normal nerve cell communication called synaptic activity.

"Blocking endocytosis isn't a viable option for treatment because cells throughout the body, including brain cells, need endocytosis for healthy function," says first author John Cirrito, Ph.D., research instructor in neurology. "But we are starting to understand the origins of amyloid beta in more detail now, and what were learning is opening other options we can pursue to seek new treatments for Alzheimer's disease."

While endocytosis is necessary for normal function of brain cells, Cirrito and others believe it may accidentally be causing the cells to take in the amyloid precursor protein (APP), which breaks down into amyloid beta. If so, a drug that reduces brain cells' intake of APP may help reduce amyloid beta production.

The results appear in the April 10 issue of Neuron.

Other research had shown previously that endocytosis might be important for amyloid beta production, and that amyloid beta is produced inside brain cells. In 2005, Cirrito and his colleagues linked increased communication between brain cells to higher amyloid beta levels.

Cirrito decided to test both endocytosis and brain cell activity in a coordinated fashion. He used a technique known as microdialysis that he had previously adapted for Alzheimer's research to monitor the results. In addition to allowing repeated sampling of the amyloid beta levels in the brains of live mice, the approach allows him to introduce drugs that reduce endocytosis and alter communication between brain cells.

When researchers gave mice the drug that stopped endocytosis, amyloid beta levels dropped by 70 percent. To see how much normal brain activity contributed to ongoing amyloid beta production in the absence of endocytosis, they then added a second drug that reduced brain cell communication. Amyloid beta levels did not decrease further.

When they reversed the experiment, reducing brain cell communication first, amyloid beta decreased by 60 percent. Adding the drug that stops endocytosis caused an additional small reduction in amyloid beta.

The results show that amyloid beta production requires both brain cell communication and endocytosis, but endocytosis is essential for a slightly larger share of amyloid beta. Basic nerve cell physiology may explain why.

The study focused on synapses, the region where nerve cells transmit messages by releasing chemicals from small compartments near the cell surface. To replenish those compartments, the nerve cell regularly takes them back in through endocytosis. The more active a brain cell is, the more often it has to bring these compartments back into the cell and refill them.

"Endocytosis can be messy in that it brings lots of substances into the cell from the membrane it internalizes," Cirrito says. "I think APP may be an innocent bystander in this process -- it just happens to be present on the cell surface when nerve cell communication causes more endocytosis. If there is a functional reason APP has to participate in this process, no one has found it."

Activity isn't the only cause of endocytosis in brain cells. The cells have other reasons for bringing in materials through endocytosis, and this additional intake could account for the small share of amyloid beta production that requires endocytosis but doesn't need brain cell activity.

Cirrito conducted the research in the laboratories of co-senior authors David M. Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and chair of the Department of Neurology at the School of Medicine, and neurologist-in-chief at Barnes-Jewish Hospital, and Steven J. Mennerick, Ph.D., associate professor of neurobiology and psychiatry.

Researchers already know several proteins on the surfaces of brain cells that bind to APP. They will be conducting follow-up studies to see if blocking these interactions can block APP endocytosis and reduce amyloid beta production.


'/>"/>

Contact: Michael Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

Related biology news :

1. Researchers identify proteins involved in new neurodegenerative syndrome
2. Texas researchers and educators head for Antarctica
3. MGH researchers describe new way to identify, evolve novel enzymes
4. University of Pennsylvania researchers develop formula to gauge risk of disease clusters
5. U of MN researchers discover noninvasive diagnostic tool for brain diseases
6. U of Minnesota researchers discover noninvasive diagnostic tool for brain diseases
7. Researchers discover new strategies for antibiotic resistance
8. Researchers find new taste in fruit flies: carbonated water
9. Binghamton University researchers investigate evolving malaria resistance
10. UIC researchers find promising new targets for antibiotics
11. Researchers develop simple method to create natural drug products
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/16/2016)... NEW YORK , May 16, 2016   ... authentication solutions, today announced the opening of an IoT ... to strengthen and expand the development of embedded ... provides an unprecedented level of convenience and security with ... to authenticate one,s identity aside from DNA. EyeLock,s platform ...
(Date:4/28/2016)... First quarter 2016:   , ... the first quarter of 2015 The gross margin was ... 18.8) and the operating margin was 40% (-13) Earnings ... flow from operations was SEK 249.9 M (21.2) , ... SEK 7,000-8,500 M. The operating margin for 2016 is ...
(Date:4/15/2016)... , April 15, 2016 ... the,  "Global Gait Biometrics Market 2016-2020,"  report to ... http://photos.prnewswire.com/prnh/20160330/349511LOGO ) , ,The global gait biometrics ... of 13.98% during the period 2016-2020. ... angles, which can be used to compute factors ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , June 23, 2016   EpiBiome , ... secured $1 million in debt financing from Silicon Valley ... up automation and to advance its drug development efforts, ... new facility. "SVB has been an incredible ... the services a traditional bank would provide," said Dr. ...
(Date:6/23/2016)... ... June 23, 2016 , ... In a new case report published today ... a patient who developed lymphedema after being treated for breast cancer benefitted from an ... paradigm for dealing with this debilitating, frequent side effect of cancer treatment. ...
(Date:6/23/2016)... , June 23, 2016 ... Hematology Review, 2016;12(1):22-8 http://doi.org/10.17925/OHR.2016.12.01.22 ... , the peer-reviewed journal from touchONCOLOGY, Andrew ... escalating cost of cancer care is placing an ... result of expensive biologic therapies. With the patents ...
(Date:6/23/2016)... (PRWEB) , ... June 23, 2016 , ... ... on quality, regulatory and technical consulting, provides a free webinar on ... on July 13, 2016 at 12pm CT at no charge. , Incomplete investigations ...
Breaking Biology Technology: