Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers Uncover Biochemical Pathway by Which Harmful Molecule May Raise Alzheimer’s Risk

A molecule implicated in Alzheimer’s disease interferes with brain cells by making them unable to “recycle” the surface receptors that respond to incoming signals, researchers at UT Southwestern Medical Center have found.

The harmful molecule, called APOE4, is present in about one out of every six people, the researchers said. Those with the gene for APOE4 have up to 10 times the risk of developing Alzheimer’s disease earlier in life than average.

The researchers discovered that APOE4 makes a nerve cell hold back the molecules that enables it to respond to other cells, thereby disabling a chemical process known to be important in learning. Their findings appear online this week in the Proceedings of the National Academy of Sciences.

“This is actually a fairly simple system,” said Dr. Joachim Herz, director of the Center for Alzheimer’s and Neurodegenerative Disease at UT Southwestern and senior author of the study. “For the first time, we see an uninterrupted biochemical pathway that links the surface of the brain cell to the dysfunction inside the cell, and specifically at the junction at which nerve cells communicate.”

The research focused on a basic characteristic of nerve cells called neurotransmission, in which they use chemicals to signal each other. When one nerve cell needs to “talk” to another, its tip sends out a chemical called a neurotransmitter. The surface of the second cell is studded with molecules called receptors, which fit specific neurotransmitters like a lock and key. When a neurotransmitter docks onto its receptor, the second cell responds.

A cell can fine-tune its sensitivity by removing receptors from its surface. To do this, the cell engulfs the receptors to its interior, taking them out of action. It can eventually recycle them back to the surface, where they can respond to neurotransmitters again.

The researchers looked at receptors that respond to a neurotransmitter called glutamate, which is implicated in memory and learning. In mice that were genetically altered to make human APOE4, the researchers found that APOE4 prevented the cells from accomplishing a vital step in learning – becoming more sensitive to repeated signals.

The researchers also studied the mice’s hippocampus – an area of the brain vital to learning – to see how it would respond to extracts from the brain of a human with Alzheimer’s. The extract prevented both normal and genetically altered mice from processing incoming signals; however, the normal mice could recover from this suppression, while the mice with APOE4 could not.

Dr. Herz and his colleagues hypothesized that APOE4 exerted its effects by interacting with the receptors for a molecule called Reelin, which keeps brain cells more sensitive to each other. Both APOE4 and Reelin bind to the same receptor. When Reelin binds to it, the combination triggers a biochemical cascade that makes the glutamate receptor more sensitive to incoming signals.

The researchers showed that APOE4 prevents the Reelin-binding receptor from being recycled back to the surface. With fewer receptors, the nerve cell can’t bind much Reelin, no matter how much is around. Without Reelin’s effects, the cell doesn’t respond as vigorously to glutamate, and doesn’t “learn” as well.

Knowing how a biological system works doesn’t automatically translate to clinical use, Dr. Herz cautioned. “Although these findings constitute a milestone in our understanding of how APOE4 becomes such a potent risk factor for Alzheimer’s disease, potential drugs that might come from this finding would still require years of development,” he said.

“The question is, now that we’ve apparently identified what’s going on, can we do anything about this disease process at the fundamental molecular level? That’s what we’re working on right now,” Dr. Herz said.

Other UT Southwestern researchers involved in the study were graduate student Ying Chen; Dr. Murat Durakoglugil, assistant instructor of molecular genetics; and Dr. Xunde Xian, postdoctoral researcher in molecular genetics.

The study was funded by the National Institutes of Health, the American Health Assistance Foundation, the Perot Family Foundation, the Consortium for Frontotemporal Dementia Research, SFB780 and the Humboldt Foundation.

Visit to learn more about UT Southwestern’s clinical services in the neurosciences, including treatment of all types of neurovascular and neuromuscular disorders.

Aline McKenzie | Newswise Science News
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

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

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>