Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Experimental drug reverses key cognitive deficits, pathology in Alzheimer’s


A new drug that enhances the activity of a key brain cell receptor involved in Alzheimer’s disease (AD) reverses learning and memory deficits in mice engineered to have pathological hallmarks of the disease. What’s more, the drug, called AF267B, reduces both of the pathologies--the brain-clogging buildup of protein "amyloid plaque" outside brain cells and the protein "neurofibrillary tangles" inside the cells.

In an article in the March 2, 2006, issue of Neuron, Dr. Frank LaFerla of the University of California, Irvine and his colleagues reported the first in vivo studies of the drug’s effects. AF267B was developed by coauthor Abraham Fisher to activate particular receptors for the neurotransmitter acetylcholine. These specific receptors, called M1 receptors, are abundant in areas of the brain--the cortex and hippocampus--known to develop severe deposits of plaques and tangles in AD patients. Dysfunction in acetylcholine receptors has been shown to be characteristic of early stages of AD.

Receptors are proteins on the neuronal surface that are triggered by the chemical signals called neurotransmitters. This triggering initiates such cellular responses as the wave of electrical excitation of a nerve impulse.

As an animal model of AD, the researchers used a "triple knockout" mouse in which three key genes involved in normal brain protein processing pathways had been knocked out, creating both amyloid plaques and neurofibrillary tangles.

In their experiments, the researchers gave the knockout mice eight weeks of daily doses of AF267B and tested the animals’ learning and memory abilities. One test involved measuring how well the treated animals could learn to find a submerged platform in a tank of murky water. This test is known to depend on the function of the hippocampus. The researchers found that the treated mice performed significantly better than untreated knockout mice on the task.

Significantly, found the researchers, the poorer performance of the untreated mice resulted from their relative inability to remember from day-to-day the location of the platform.

In another memory test, however, the treated mice did not show improved performance compared to untreated mice. In this test--which depends on the function of another Alzheimer’s-affected brain region called the amygdala--the mice were required to learn to associate a dark chamber with an unpleasant shock.

Analyzing the brain tissue of the untreated and treated mice, the researchers found that treatment with AF267B reduced levels of both pathological plaques and tangles in the cortex and hippocampus, but not in the amygdala.

In experiments that demonstrated the central role of M1 receptors in AD-like pathology, the researchers also tested the effects on the mice of another drug, dicyclomine, that blocks M1 receptors. They found that both normal and knockout mice treated with the drug showed the characteristic learning and memory impairments, as well as amyloid and tangle pathologies.

The researchers also studied the effects of AF267B treatment on key enzymes involved in amyloid protein processing in the cell. They found evidence that the drug appears to work by affecting levels of these enzymes, as a result of its enhancement of M1 receptor activity.

The researchers concluded that "the results of the present study show the remarkable therapeutic potential of AF267B in attenuating the major hallmark neuropathological lesions relevant to AD and in restoring cognitive function, at least for certain tasks." They also pointed out the importance of the finding that administering dicyclomine to block M1 receptors exacerbated the disease pathologies.

"Further work, including clinical trials in humans, will be necessary to determine if this new generation of M1 agonists will produce a similar therapeutic efficacy as was observed in the [knockout] mice," they concluded.

Heidi Hardman | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

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

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

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

27.10.2016 | Life Sciences

More VideoLinks >>>