Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Toxic protein could explain Alzheimer’s and lead to breakthroughs

19.08.2003


Researchers at Northwestern University have discovered for the first time in humans the presence of a toxic protein that they believe to be responsible for the devastating memory loss found in individuals suffering from Alzheimer’s disease.



An understanding of this key molecular link in the progression of Alzheimer’s could lead to the development of new therapeutic drugs capable of reversing memory loss in patients who are treated early, in addition to preventing or delaying the disease. Help for individuals with pre-Alzheimer’s memory failure (mild cognitive impairment) also is envisioned. The findings will be published online by the Proceedings of the National Academy of Sciences during the week of Aug. 18.

The research team, led by William L. Klein, professor of neurobiology and physiology, found up to 70 times more small, soluble aggregated proteins called "amyloid b-derived diffusible ligands" (ADDLs, pronounced "addles") in the brain tissue of individuals with Alzheimer’s disease compared to that of normal individuals.


The clinical data strongly support a recent theory in which ADDLs accumulate at the beginning of Alzheimer’s disease and block memory function by a process predicted to be reversible. ADDLs have the ability to attack the memory-building activity of synapses, points of communication where neurons exchange information, without killing neurons.

"Researchers for more than a decade thought it was big molecules, the ’amyloid fibrils,’ that caused memory problems, but we think the real culprits are extremely small molecules, what we call ADDLs," said Klein, who is a member of Northwestern’s Cognitive Neurology and Alzheimer’s Disease Center. "Now we’ve shown that ADDLs are present in humans and are a clinically valid part of Alzheimer’s pathology. If we can develop drugs that target and neutralize these neurotoxins, it might be possible to not only slow down memory loss, but to actually reverse it, to bring memory function back to normal."

Although both are a form of amyloid beta, ADDLs and their properties differ significantly from the amyloid fibrils (known as plaques) that are a diagnostic hallmark of Alzheimer’s. ADDLs found in human brains, mostly 12 or 24 amyloid beta proteins clumped together, are tiny and undetectable in conventional neuropathology; fibrils are much, much larger. While fibrils are immobile toxic waste dumps, ADDLs are soluble and diffuse between brain cells until they find vulnerable synapses. (Single pieces of amyloid beta protein in the brain is normal.)

"The difference between ADDLs and fibrils is like comparing four eggs, over easy, to an enormous omelet that could feed the entire Chicago Bears team," said Klein. ""You start with eggs, but the final product taste, texture and size are all different."

The existence of ADDLs may help explain the poor correlation between plaques and neurological deficits. Studies by other researchers have shown a reversal of memory failure in mouse models treated with amyloid beta antibodies -- but without any reduction in plaque. The antibodies appear to restore memory because they neutralize ADDLs, which Klein’s group has found in mouse models with Alzheimer’s as well as in human brains with Alzheimer’s.

Klein’s research team recently began a study funded by the National Institutes of Health to continue investigating ADDLs in humans and further characterize these molecules. In addition to Alzheimer’s disease, ADDL-like molecules could be the cause of other degenerative diseases.

Klein also is working with researchers at Northwestern’s Institute for Nanotechnology on clinical diagnostics capable of detecting ADDLs in blood or cerebral spinal fluid. Currently diagnosis of Alzheimer’s is based primarily on a battery of psychological tests.

"Now that ADDLs have been discovered in humans we would like to develop effective diagnostics and that means employing nanotechnology," said Klein. "That’s because ADDLs are present in very low concentrations, and nanotechnology has the potential to provide the ultra-sensitive assays needed for the clinic."

Klein, Grant A. Krafft, formerly at Northwestern University Medical School and now chief scientific officer at Acumen Pharmaceuticals, Inc., and Caleb E. Finch, professor of biological sciences and gerontology at the University of Southern California, reported the discovery of ADDLs in 1998. Krafft and Finch are co-authors on the PNAS paper. Northwestern and USC hold joint patents on the composition and use of ADDLs in neurodisorders.

The patent rights have been licensed to Acumen Pharmaceuticals, based in Glenview, Ill., for the development of drugs that treat Alzheimer’s disease and other memory-related disorders. Clinical trials could be two or three years away.

In addition to Klein, Krafft and Finch, other authors on the paper are Yuesong Gong (lead author), Lei Chang, Kirsten L. Viola, Pascale N. Lacor and Mary P. Lambert, from Northwestern University.


The research was supported by the National Institutes of Health, the Boothroyd, Feiger and French foundations, and the Institute for the Study of Aging.

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

More articles from Health and Medicine:

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

nachricht What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego

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: 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...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

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

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>