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Scientists demonstrate means of reducing Alzheimer's-like plaques in fly brain
Date:7/15/2008

Neuroscientists at Cold Spring Harbor Laboratory (CSHL) are part of a collaboration that has succeeded in demonstrating that overexpression of an enzyme in the brain can reduce telltale deposits causally linked with Alzheimer's disease.

CSHL Professor Yi Zhong, Ph.D., whose lab studies genetic mechanisms involved in neurodegenerative illnesses, helped develop a line of transgenic fruit flies that was central in the experiments. Transgenic organisms express genes that occur naturally in other species. In this instance, the fruit flies were engineered to express a human gene that codes for the production of an enzyme called neprilysin, or NEP.

Beta amyloid and the pathology of Alzheimer's

NEP enzymes are known from prior experiments to degrade protein deposits in the brain that are characteristic of Alzheimer's . The protein clumps -- sheet-like plaques between brain cells called beta amyloid deposits -- have been found in the autopsied brains of human Alzheimer's patients.

Two types of beta amyloid sheets are associated with Alzheimer's plaques. Scientists have suspected that so-called Aβ42 plaques -- those structurally composed of 42-amino acid beta amyloid peptides -- are involved in the genesis of the illness. "But the mechanism by which Aβ42 reaches pathological levels in the brains of late-onset patients is not well understood," Dr. Zhong explained.

Past experiments in transgenic mice expressing human beta amyloid had shown that a deficiency of NEP caused a series of serious problems. The deficiency accelerated the formation of amyloid plaques, caused dysfunction in the synapses, or gaps, across which nerve cells in the brain communicate, and caused memory defects.

Reversing the process: mixed results

In new experiments, Dr. Zhong and other team members, who include Kanae Iijima-Ando, Ph.D., of the Farber Institute for Neurosciences and neuroscientists from
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Contact: Jim Bono
bono@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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