Amyloid assembly and cerebral endothelial cells response

Agueda Rostagno, PhD
NYU School of Medicine (New York, NY)
Year Awarded:
2004
Grant Duration:
April 1, 2004 to March 31, 2006
Disease:
Alzheimer's Disease
Award Amount:
$299,959
Grant Reference ID:
A2004017
Award Type:
Standard
Award Region:
US Northeastern

Amyloid assembly and cerebral endothelial cells response

Details


Cerebral Amyloid Angiopathy (CAA) is the generic name for a large group of diseases characterized by the presence of amyloid beta fibrils (Aß) in small vessels and medium-sized arteries and arterioles in the brain. Although Aß is the most common CAA amyloid, many other proteins have been associated with the formation of amyloid deposits in the brain. Some of these proteins are cystatin C, transthyretin, gelsolin, and the recently described ABri and ADan peptides. The ABri and ADan peptides are associated with two rare hereditary conditions—familial British and Danish dementias—that are characterized by extensive CAA and Alzheimer's-like neurodegeneration. This is an indication that different amyloid molecules may lead to the same scenario of neuronal loss and dementia. Dr. Rostagno's is working with fibrils and pre-fibrils of various amyloid molecules and the hereditary variants involved in the production of CAA in cultures. These compounds will be fed to human cerebral endothelial cells in culture, and their toxicity as well as their ability to induce inflammation will be assessed by biochemical analysis. It is hoped that an understanding of the molecular events triggered by the toxic peptides will lead to the design and development of new treatments to modulate these cellular processes and ameliorate the impact of these neurological diseases.

Publications

Lashley, T., Revesz, T., Plant, G., Bandopadhyay, R., Lees, A.J., Frangione, B., Wood, N.W., de Silva, R., Ghiso, J., Rostagno, A. and Holton, J.L. (2008) Expression of BRI2 mRNA and protein in normal human brain and familial British dementia: its relevance to the pathogenesis of disease. Neuropathol Appl Neurobiol. 2008 Oct;34(5):492-505. Epub 2008 Feb 13.  

Rostagno, A., Lashley, T., Ng, D., Meyerson, J., Braendgaard, H., Plant, G., Bojsen-Moller, M., Holton, J., Frangione, B., Revesz, T., Ghiso, J. (2007) Preferential association of serum amyloid P component with fibrillar deposits in familial British and Danish dementias: similarities with Alzheimer's disease. J Neurol Sci. 257(1-2):88-96.  

Lashley, T., Holton, J.L., Verbeek, M.M., Rostagno, A., Bojsen-Moller, M., David, G., van Horssen, J., Braendgaard, H., Plant, G., Frangione, B., Ghiso, J., Revesz, T. (2006) Molecular chaperons, amyloid and preamyloid lesions in the BRI2 gene-related dementias: a morphological study. Neuropathol Appl Neurobiol. 32(5):492-504.  

Ghiso, J., Rostagno, A., Tomidokoro, Y., Lashley, T., Bojsen-Moller, M., Braendgaard, H., Plant, G., Holton, J., Lal, R., Revesz, T. and Frangione, B. (2006) Genetic alterations of the BRI2 gene: familial British and Danish dementias. Brain Pathol. 16(1):71-79.  

Rostagno, A., Tomidokoro, Y., Lashley, T., Ng, D., Plant, G., Holton, J., Frangione, B., Revesz, T. and Ghiso, J. (2005) Chromosome 13 dementias. Cell Mol Life Sci. 62(16):1814-1825.  

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