New mechanism for amyloid beta protein's toxic impact on the Alzheimer's brain

Jun 24, 2009

Scientists have uncovered a novel mechanism linking soluble amyloid -- protein with the synaptic injury and memory loss associated with Alzheimer's disease (AD). The research, published by Cell Press in the June 25 issue of the journal Neuron, provides critical new insight into disease pathogenesis and reveals signaling molecules that may serve as potential additional therapeutic targets for AD.

Amyloid beta protein plays a major pathogenic role in AD, a devastating characterized by progressive cognitive impairment and memory loss. "Given the mounting evidence that small soluble A-beta assemblies mediate synaptic impairment in AD, elucidating the precise by which this occurs has important implications for treating and preventing the disease," explains senior study author, Dr. Dennis Selkoe from the Center for Neurologic Diseases at Brigham and Women's Hospital and Harvard Medical School.

Dr. Selkoe, Dr. Shaomin Li, and colleagues examined regulation of a cellular communication phenomenon known as long-term synaptic depression (LTD). LTD has been linked with , but a role for A-beta in the regulation of LTD has not been clearly described. The researchers found that soluble A-beta facilitated LTD in the hippocampus, a region of the brain intimately associated with memory. The enhanced synaptic depression induced by soluble A-beta was mediated through a decrease in glutamate recycling at hippocampal synapses.

Excess glutamate, the major excitatory neurotransmitter in the brain, is thought to contribute to the progressive neuronal loss characteristic of AD. The researchers went on to show that A-beta-enhanced LTD was mediated by glutamate receptor activity and that the LTD could be prevented by an extracellular glutamate scavenger system. A very similar enhancement of LTD could be induced by a pharmacological blocker of glutamate reuptake. Importantly, soluble A-beta directly and significantly decreased glutamate uptake by isolated synapses.

"Our findings provide evidence that soluble A-beta from several sources enhances synaptic depression through a novel mechanism involving altered glutamate uptake at hippocampal synapses," concludes Dr. Selkoe. "These results have both mechanistic and therapeutic implications for the initiation of hippocampal synaptic failure in AD and in more subtle forms of age-related A? accumulation." Future studies are needed to determine precisely how soluble A-beta protein physically interferes with transporters at the synapse.

Source: Cell Press (news : web)

Explore further: New treatments for cancer, diabetes, and heart disease—you may have a pig to thank

add to favorites email to friend print save as pdf

Related Stories

How is our left brain is different from our right?

Nov 17, 2008

Since the historical discovery of the speech center in the left cortex in 150 years ago, functional differences between left and right hemisphere have been well known; language is mainly handled by left hemisphere, while ...

Ionophore reverses Alzheimer's within days in mouse models

Jul 09, 2008

Scientists report a remarkable improvement in Alzheimer's transgenic mice following treatment with a new drug. The study, published by Cell Press in the July 10th issue of the journal Neuron, provides the first demonstration that a ...

Astrocytes and synaptic plasticity

Oct 13, 2008

By mopping up excess neurotrophic factor from neuronal synapses, astrocytes may finely tune synaptic transmission to affect processes such as learning and memory, say Bergami et al.

Mechanism explains calcium abnormalities in Alzheimer's brain

Jun 25, 2008

A new study uncovers a mechanism that directly links mutations that cause early onset Alzheimer's disease (AD) with aberrant calcium signaling. The research, published by Cell Press in the June 26th issue of the journal Neuron, provid ...

Recommended for you

Educating on sickle cell risk

1 hour ago

Members of the public in sub-Saharan Africa who are carriers of the hereditary disease sickle cell disease must be educated aggressively through public health campaigns to raise awareness of the risks of parenting offspring ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.