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Alzheimer's: Newly identified protein pathology impairs RNA splicing
Date:9/10/2013

hey were aided by collaborators at University of Kentucky, Rush University, and University of Washington as well as colleagues at Emory.

Accumulations of plaques and tangles in the brains of patients with Alzheimer's disease were first observed more than a century ago. Investigating the proteins in these pathological structures has been central to the study of the disease.

Most experimental treatments for Alzheimer's have aimed at curbing beta-amyloid, an apparently toxic protein fragment that is the dominant component of amyloid plaques. Other approaches target the abnormal accumulation of the protein tau in neurofibrillary tangles. Yet the development of Alzheimer's is not solely explained by amyloid and tau pathologies, Lah says.

"Two individuals may harbor similar amounts of amyloid plaques and tau tangles in their brains, but one may be completely healthy while the other may have severe memory loss and dementia," he says.

These discrepancies led Emory investigators to take a "back to basics" proteomics approach, cataloguing the proteins that make up insoluble deposits in the brains of Alzheimer's patients.

"The Alzheimer's field has been very focused on amyloid and tau, and we wanted to use today's proteomics technologies to take a comprehensive, unbiased approach," Levey says.

The team identified 36 proteins that were much more abundant in the detergent-resistant deposits in brain tissue from Alzheimer's patients. This list included the usual suspects: tau and beta-amyloid. Also on the list were several "U1 snRNP" proteins, which are involved in RNA splicing.

These U1 proteins are normally seen in the nucleus of normal cells, but in Alzheimer's brains they accumulated in tangle-like structures. Accumulation of insoluble U1 protein was seen in samples from patients with mild cognitive impairment (MCI), a precursor stage to Alzheimer's, but the U1 pathology was not seen in any other brain diseases th
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Contact: Holly Korschun
404-727-3990
Emory Health Sciences
Source:Eurekalert

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