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Study outlines how stroke, head injury can increase risk of Alzheimer's disease

Researchers from the MassGeneral Institute for Neurodegenerative Disorders (MGH-MIND) have discovered how the death of brain cells caused by a stroke or head injury may cause generation of amyloid-beta protein the key component of senile plaques seen in the brains of patients with Alzheimer's disease. Their report appears in the June 7 issue of the journal Neuron.

We have discovered how a stroke can trigger a series of biochemical events that increase amyloid-beta production in the brain, says Giuseppina Tesco, MD, PhD, of the MGH-MIND Genetics and Aging Research Unit, the papers lead author. These findings raise the prospect of novel therapies that could interfere with this process and reduce the risk of Alzheimers disease in stroke or head trauma patients.

It has been known for several years that strokes and head injuries can increase the risk of Alzheimers disease, but the mechanism underlying that increased risk has not been understood. Alzheimer's disease is characterized by plaques within the brain of amyloid-beta protein, which is toxic to brain cells. Amyloid-beta is formed when the larger amyloid precursor protein (APP) is clipped by two enzymes beta-secretase, also known as BACE, and gamma-secretase which releases the amyloid-beta fragment. The usual processing of APP by an enzyme called alpha-secretase produces an alternative, non-toxic protein.

The MGH-MIND team previously reported that cellular BACE levels are normally controlled by the enzymes breakdown in compartments called lysosomes, a process that is disrupted if a molecular signal on the enzyme is altered. That signal binds to GGA proteins, which are required for the transport of several types of enzymes into lysosomes. One of these proteins, GGA3, can be degraded by caspase, an enzyme takes part in the cell-death process called apoptosis.

In a series of experiments the MGH-MIND researchers revealed how cell death caused by a brain injury,
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
6-Jun-2007


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