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Tiny but toxic: MBL researchers discover a mechanism of neurodegeneration in Alzheimer's disease

WOODS HOLE, MATiny, toxic protein particles severely disrupt neurotransmission and inhibit delivery of key proteins in Alzheimer's disease, two separate studies by Marine Biological Laboratory (MBL) researchers have found.

The particles are minute clumps of amyloid beta, which has long been known to accumulate and form plaques in the brain of Alzheimer's patients.

"These small particles that haven't aggregated into plaquesthese are increasingly being seen as the really toxic species of amyloid beta," says Scott Brady of University of Illinois College of Medicine, who has been an MBL investigator since 1982.

Brady and his colleagues found that these particles inhibit neurons from communicating with each other and with other target cells in the body.

"The disease symptoms for Alzheimer's are associated not with the death of the neurons that is a very late event but with the loss of functional connections. It's when the neuron is no longer talking to its targets that you start to get the memory deficits and dementia associated with the disease," Brady says.

The amyloid beta particles activate an enzyme, CK2, which in turn disrupts the "fast axonal transport" system inside the neuron, Brady found. This transport system has motor proteins that move various kinds of cargo (including neurotransmitters and the associated protein machinery for their release) from place to place in the neuron on microtubule tracks.

Brady's findings are complemented by a new study by Rudolfo Llins of New York University School of Medicine. Brady and Llins both conduct neuroscience research at the MBL using the giant nerve cell of the Woods Hole squid, Loligo paeleii, as a model system.

Llins found that activation of CK2 blocks neurotransmission at the synapse the point where the neuron connects to its target.

"Disruptions in the fast axonal transport system are probably key elements in the pathogenesis of Alzhe

Contact: Diana Kenney
Marine Biological Laboratory

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Tiny but toxic: MBL researchers discover a mechanism of neurodegeneration in Alzheimer's disease
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