Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery supports theory of Alzheimer's disease as form of diabetes

28.09.2007
Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a novel third form of diabetes.

Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer’s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer’s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for “amyloid ß-derived diffusible ligand.”)

With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer’s disease, the Northwestern study sheds light on the emerging idea of Alzheimer’s being a “type 3” diabetes.

The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer’s. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)

In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer’s disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.

“We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,” said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. “Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer’s disease.”

ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer’s disease and block memory function by a process predicted to be reversible.

In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.

“We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer’s brains,” said Klein, a member of Northwestern’s Cognitive Neurology and Alzheimer's Disease Center. “We’re dealing with a fundamental new connection between two fields, diabetes and Alzheimer’s disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.”

Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.

They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.

“In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding,” said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein’s lab. “These factors suggest that insulin resistance in the brains of those with Alzheimer’s is a response to ADDLs.”

“With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer’s treatment,” said Klein. “I think such drugs could supercede currently available Alzheimer’s drugs.”

Megan Fellman | EurekAlert!
Further information:
http://www.northwestern.edu

Further reports about: ADDL Alzheimer Diabetes Insulin Synapse binding individuals nerve cells neurons resistant

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>