Immunohistochemical distribution of amyloid deposits in 25 cows diagnosed with systemic AA amyloidosis
ABSTRACT The distribution of amyloid deposits was histopathologically and immunohistochemically examined in 25 cows aged 5 to 10 years that had been diagnosed with systemic AA amyloidosis. This examination revealed that amyloid deposits were also present in the hypophysis, ovary, uterus, mammary gland and skeletal muscle, in addition to the liver, kidney, spleen, pancreas, thyroid gland, adrenal gland, gastrointestinal mucosa, heart, lung and lymph nodes. The examined cows tended to have chronic inflammations, including chronic mastitis (six cases) or chronic pneumonia (four cases), which is thought of as a causative agent of AA amyloidosis. In contrast, five cases did not exhibit any chronic inflammation.
SourceAvailable from: Tomoaki Murakami[Show abstract] [Hide abstract]
ABSTRACT: Amyloidosis is a collective term for a group of disorders that induce functional impairment of organs and occurs through the accumulation of amyloid, or misfolded protein in beta-sheets. AA amyloidosis is a lethal systemic amyloidosis with SAA as the precursor protein, and is observed in various animal species, including humans. AA amyloidosis can be induced artificially by continuously administering inflammatory stimuli in experimental animal models. In this process of experimental induction, the administration of AA amyloids from either the same or different species is known to markedly expedite AA amyloidosis development, and this is also termed transmission of AA amyloidosis. Similarly to prion disease, AA amyloidosis is considered to be transmitted via a "seeding-nucleation" process. In this manuscript, we reviewed the pathology and transmissibility of AA amyloidosis in animals. Copyright © 2014. Published by Elsevier B.V.Virus Research 12/2014; DOI:10.1016/j.virusres.2014.12.019 · 2.83 Impact Factor
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ABSTRACT: Pathologic amyloid accumulates in the CNS or in peripheral organs, yet the mechanism underlying the targeting of systemic amyloid deposits is unclear. Serum amyloid A (SAA) 1 and 2 are produced predominantly by the liver and form amyloid most commonly in the spleen, liver, and kidney. In contrast, SAA3 is produced primarily extrahepatically and has no causal link to amyloid formation. Here, we identified 8 amyloidosis cases with amyloid composed of SAA3 expanding the uterine wall of goats with near-term fetuses. Uterine amyloid accumulated in the endometrium, only at the site of placental attachment, compromising maternal-fetal gas and nutrient exchange and leading to fetal ischemia and death. No other organ contained amyloid. SAA3 mRNA levels in the uterine endometrium were as high as SAA2 in the liver, yet mass spectrometry of the insoluble uterine peptides identified SAA3 as the predominant protein, and not SAA1 or SAA2. These findings suggest that high local SAA3 production led to deposition at this unusual site. Although amyloid A (AA) amyloid deposits typically consist of an N-terminal fragment of SAA1 or SAA2, here, abundant C-terminal peptides indicated that the uterine amyloid was largely composed of full-length SAA3. The exclusive deposition of SAA3 amyloid in the uterus, together with elevated uterine SAA3 transcripts, suggests that the uterine amyloid deposits were due to locally produced SAA3. This is the first report of SAA3 as a cause of amyloidosis and of AA amyloid deposited exclusively in the uterus.-Gaffney, P. M., Barr, B., Rowe, J. D., Bett, C., Drygiannakis, I., Giannitti, F., Trejo, M., Ghassemian, M., Martin, P., Masliah, E., Sigurdson, C. J. Protein profiling of isolated uterine AA amyloidosis causing fetal death in goats. © FASEB.The FASEB Journal 11/2014; DOI:10.1096/fj.14-256081 · 5.48 Impact Factor
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ABSTRACT: Transmissible spongiform encephalopaties (TSEs) are fatal neurodegenerative diseases characterized by the aggregation and accumulation of the misfolded prion protein in the brain. Other proteins such as β-amyloid, tau or Serum Amyloid-A (SAA) seem to share with prions some aspects of their pathogenic mechanism; causing a variety of so called prion-like diseases in humans and/or animals such as Alzheimer's, Parkinson's, Huntington's, Type II diabetes mellitus or amyloidosis. The question remains whether these misfolding proteins have the ability to self-propagate and transmit in a similar manner to prions. In this review, we describe the prion and prion-like diseases affecting animals as well as the recent findings suggesting the prion-like transmissibility of certain non-prion proteins. Copyright © 2014. Published by Elsevier B.V.Virus Research 11/2014; DOI:10.1016/j.virusres.2014.11.026 · 2.83 Impact Factor