P01.34

Pathological Interaction Between Protein Misfolding Disorders: Prions and
Alzheimer's Disease

Morales, R; Estrada, L; Castilla, J; Soto, C
University of Texas Medical Branch, Neurology, USA

Protein Misfolding Disorders (PMD) include several diverse diseases, such Alzheimer's,
Parkinson's, Transmissible Spongiform Encephalopathies, Diabetes Type II and various
systemic amyloidosis. The central event in these diseases is the accumulation of a
misfolded, ß-sheet rich aggregated form of a naturally expressed protein. In vitro
studies have shown that protein misfolding and aggregation follows a seedingnucleation
mechanism similar to the process of crystallization. In this model, the
limiting step is the formation of small oligomeric intermediates that act as seeds to
catalyze the polymerization process. The seeding-nucleation model provides a
rationale and plausible explanation for the infectious nature of prions. Infectivity lies on
the capacity of preformed stable misfolded oligomeric proteins to act as a seed to
catalyze the misfolding and aggregation process. The mechanism of misfolding
and aggregation is similar in all PMD suggesting that misfolded aggregates have
an inherent capability to be transmissible. Moreover, it has been shown that
oligomeric seeds formed by one protein can accelerate the misfolding and aggregation of
another protein, by a process termed cross-seeding. Our current study aims to assess
the potential molecular cross-talk among PMD in vivo. For this purpose we inoculated with
prions a transgenic mice model of Alzheimer's disease (tg2576) that develops typical
amyloid plaques over time. 45, 303 and 365 days old transgenic and wild type mice
were inoculated intraperitoneally with RML prions. We found significant diminution in
prion incubation periods for tg2576 mice compared to age matched wild type controls.
Moreover, a time dependent effect was observed, where the shorter incubation period
was observed in animals containing larger number of amyloid plaques. Inoculation of
tg2576-RML prions into wild type mice showed incubation periods similar to the
original infectious material, suggesting that strains characteristics are maintained. In
vitro data showed cross-seeding aggregation between PrPSc and Aß. Our findings
suggest an interaction between Alzheimer's and prion pathologies, indicating
that one protein misfolding process may be an important risk factor for the
development of a second perhaps more prevalent disease.

http://www.prion2007.com/pdf/Prion%2...0Abstracts.pdf


CREUTZFELDT JAKOB DISEASE MAD COW BASE, CWD, SCRAPIE UPDATE OCT 2007


http://cjdmadcowbaseoct2007.blogspot.com/


Transmissible Spongiform Encephalopathy UPDATE USA OCTOBER 2007

http://www.phxnews.com/fullstory.php?article=53128



October 2007 Update on Feed Enforcement Activities to Limit the Spread of
BSE

http://www.phxnews.com/fullstory.php?article=53149




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