Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Two proteins may help prevent Alzheimer’s brain plaques


A study led by researchers at Washington University School of Medicine in St. Louis suggests two proteins work together in mice to prevent formation of brain plaques characteristic of Alzheimer’s disease.

The proteins, apolipoprotein E (apoE) and clusterin, appear to act as "chaperones" orchestrating the clearance of potentially hazardous molecules out of the brain. Ironically, these proteins also have been implicated in a key stage of plaque formation. The study appears in the Jan. 22 issue of the journal Neuron.

"This is one of the first demonstrations in living animals that these proteins affect amyloid clearance," says David H. Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "Our findings suggest it is worthwhile to explore the use of drugs or therapies to alter or perhaps increase the expression of these proteins as a potential treatment for Alzheimer’s disease."

Holtzman, who also is the Charlotte and Paul Hagemann Professor of Neurology and professor of molecular biology and pharmacology, led the study; Ronald DeMattos, Ph.D., formerly an instructor in neurology, and John R. Cirrito, a graduate student in neuroscience, are co-first authors. The team collaborated with Eli Lilly and Company, where DeMattos now works.

A key step in the development of Alzheimer’s disease is the formation of brain plaques. Studies suggest these plaques form when the protein amyloid beta (Abeta) is converted from its soluble to its insoluble form and coalesces into hair-shaped threads called fibrils. Unable to dissolve or be cleared out of the brain, the fibrils eventually clump together and become the amyloid plaques that are a hallmark of Alzheimer’s.

In previous studies, Holtzman’s team was instrumental in showing both apoE and clusterin promote the formation of these fibrils. Their new paper confirms that in mice genetically engineered to develop Alzheimer’s disease-like brain plaques, those without either apoE or clusterin developed fewer fibrils.

The team therefore expected mice lacking both proteins would develop even fewer deposits. However, the opposite was true. Moreover, fibrils in animals lacking both proteins developed significantly earlier in life and resulted in the more advanced amyloid plaques. Such extreme Abeta deposition at a young age is akin to that in humans with the rare, genetic form of the disease called familial Alzheimer’s.

"This was an unexpected and striking result," Holtzman says. "Though at first counter-intuitive, it implies that apoE and clusterin cooperate to suppress Abeta deposition."

In addition to increased amounts of Abeta in brain tissue, the team also found abnormally high levels in the fluid surrounding individual brain cells and in the fluid surrounding the entire brain. In contrast, levels of Abeta in the blood were not abnormally high.

Combined, the results suggest the two proteins not only play a role in the development of fibrils, but also in the clearance of Abeta from brain tissue and surrounding fluid. Without its chaperones, Abeta protein settles in the brain and eventually clusters into plaques.

According to Holtzman, the next step is to determine whether human forms of apoE and clusterin also delay or prevent the development of plaques in the mouse model and to explore the potential for drugs or gene therapy to reverse plaque formation in mice.

DeMattos RB, Cirrito JR, Parsadanian M, May PC, O’Dell MA, Tayler JW, Harmony JAK, Aronow BJ, Bales KR, Paul SM, Holtzman DM. ApoE and clusterin cooperatively suppress Abeta levels and deposition: Evidence at apoE regulates extracellular Abeta metabolism in vivo. Neuron, Jan. 22, 2004.

Funding from the National Institutes of Health, MetLife Foundation and Eli Lilly and Company supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Gila Z. Reckess | WUSTL
Further information:

More articles from Health and Medicine:

nachricht Advanced analysis of brain structure shape may track progression to Alzheimer's disease
26.10.2016 | Massachusetts General Hospital

nachricht Indian roadside refuse fires produce toxic rainbow
26.10.2016 | Duke University

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: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

Gene therapy shows promise for treating Niemann-Pick disease type C1

27.10.2016 | Life Sciences

Solid progress in carbon capture

27.10.2016 | Power and Electrical Engineering

More VideoLinks >>>