Induction of AApoAII amyloidosis by various heterogeneous amyloid fibrils

Fu, Xiaoying; Korenaga, Tatsumi; Fu, Li; Xing, Yanming; Guo, Zhanjun; Matsushita, Takatoshi; Hosokawa, Masanori; Naiki, Hironobu; Baba, Satoshi; Kawata, Yasushi; Ikeda, Shu Ichi; Ishihara, Tokuhiro; Mori, Masayuki; Higuchi, Kenichi

doi:10.1016/s0014-5793(04)00295-9

Cited by 39 publications

(28 citation statements)

References 27 publications

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“…13,14 Injection of various kinds of amyloid fibrils into R1.P1-Apoa2 c mice also induced amyloidosis. 15 These results demonstrated that a common amyloid fibril structure could serve as a seed for amyloid fibril formation (cross-seeding) in vivo. Prion-like transmission was also reported in mouse inflammation-associated amyloid A (AA) amyloidosis.…”

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confidence: 72%

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

Yao

et al. 2007

Laboratory Investigation

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In mice, apolipoprotein A-II (apoA-II) self-associates to form amyloid fibrils (AApoAII) in an age-associated manner. We postulated that the two most important factors in apoA-II amyloidosis are the Apoa2 c allele, which codes for the amyloidogenic protein APOA2C (Gln5, Ala38) and transmission of amyloid fibrils. To characterize further the contribution of the Apoa2 c allele to amyloidogenesis and improve detection of amyloidogenic materials, we established transgenic mice that overexpress APOA2C protein under the cytomegalovirus (CMV) immediate early gene (CMV-IE) enhancer/ chicken b promoter. Compared to transgene negative (Tg À/À ) mice that express apoA-II protein mainly in the liver, mice homozygous (Tg þ / þ ) and heterozygous (Tg þ /À ) for the transgene express a high level of apoA-II protein in many tissues. They also have higher plasma concentrations of apoA-II, higher ratios of ApoA-II/apolipoprotein A-I (ApoA-I) and higher concentrations of high-density lipoprotein (HDL) cholesterol. Following injection of AApoAII fibrils into Tg þ / þ mice, amyloid deposition was observed in the testis, liver, kidney, heart, lungs, spleen, tongue, stomach and intestine but not in the brain. In Tg þ / þ mice, but not in Tg À/À mice, amyloid deposition was induced by injection of less than 10 À8 mg AApoAII fibrils. Furthermore, deposition in Tg þ / þ mice occurred more rapidly and to a greater extent than in Tg À/À mice. These studies indicate that increased levels of APOA2C protein lead to earlier and greater amyloid deposition and enhanced sensitivity to the transmission of amyloid fibrils in transgenic mice. This transgenic mouse model should prove valuable for studies of amyloidosis.

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confidence: 72%

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

Yao

et al. 2007

Laboratory Investigation

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“…However, in theory, any particle that can mimic the ␤-amyloid-inducing activity of A␤ from brain extracts could trigger the process of amyloid induction. It has been shown that the induction of amyloid A amyloidosis can be triggered in Tg mice by heteronucleants such as silk (39,40), and heteronucleation of apolipoprotein AII amyloidosis also has been demonstrated in mice (41). In light of the fact that the vast majority of AD cases are idiopathic in nature, a brain-penetrant environmental factor with A␤-nucleating properties remains a potential candidate for the initiation of the A␤ cascade (8).…”

Section: Discussionmentioning

confidence: 99%

Induction of cerebral β-amyloidosis: Intracerebral versus systemic Aβ inoculation

Eisele

Bolmont

Heikenwälder

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

262

248

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Despite the importance of the aberrant polymerization of A␤ in the early pathogenic cascade of Alzheimer's disease, little is known about the induction of A␤ aggregation in vivo. Here we show that induction of cerebral ␤-amyloidosis can be achieved in many different brain areas of APP23 transgenic mice through the injection of dilute A␤-containing brain extracts. Once the amyloidogenic process has been exogenously induced, the nature of the induced A␤-deposition is determined by the brain region of the host. Because these observations are reminiscent of a prion-like mechanism, we then investigated whether cerebral ␤-amyloidosis also can be induced by peripheral and systemic inoculations or by the intracerebral implantation of stainless steel wires previously coated with minute amounts of A␤-containing brain extract. Results reveal that oral, intravenous, intraocular, and intranasal inoculations yielded no detectable induction of cerebral ␤-amyloidosis in APP23 transgenic mice. In contrast, transmission of cerebral ␤-amyloidosis through the A␤-contaminated steel wires was demonstrated. Notably, plasma sterilization, but not boiling of the wires before implantation, prevented the induction of ␤-amyloidosis. Our results suggest that minute amounts of A␤-containing brain material in direct contact with the CNS can induce cerebral ␤-amyloidosis, but that systemic cellular mechanisms of prion uptake and transport to the CNS may not apply to A␤.Alzheimer's disease ͉ amyloid ͉ prion ͉ sterilization ͉ transmission

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“…In addition to foie gras, meat derived from sheep (16) and seemingly healthy cattle (17) may represent other dietary sources of this material. Further, the fact that chemically heterologous fibrils can serve as AEF, as demonstrated in experimental models of AA (18)(19)(20) and AApoAII amyloidosis (21)(22)(23), suggests that it may be hazardous for individuals who are prone to develop other types of amyloid-associated disorders, e.g., Alzheimer's disease or type II diabetes, to consume such products.…”

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confidence: 99%

Amyloidogenic potential of foie gras

Solomon

Richey

Murphy

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

117

103

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The human cerebral and systemic amyloidoses and prionassociated spongiform encephalopathies are acquired or inherited protein folding disorders in which normally soluble proteins or peptides are converted into fibrillar aggregates. This is a nucleation-dependent process that can be initiated or accelerated by fibril seeds formed from homologous or heterologous amyloidogenic precursors that serve as an amyloid enhancing factor (AEF) and has pathogenic significance in that disease may be transmitted by oral ingestion or parenteral administration of these conformationally altered components. Except for infected brain tissue, specific dietary sources of AEF have not been identified. Here we report that commercially available duck-or goose-derived foie gras contains birefringent congophilic fibrillar material composed of serum amyloid A-related protein that acted as a potent AEF in a transgenic murine model of secondary (amyloid A protein) amyloidosis. When such mice were injected with or fed amyloid extracted from foie gras, the animals developed extensive systemic pathological deposits. These experimental data provide evidence that an amyloid-containing food product hastened the development of amyloid protein A amyloidosis in a susceptible population. On this basis, we posit that this and perhaps other forms of amyloidosis may be transmissible, akin to the infectious nature of prion-related illnesses.amyloid protein A amyloidosis ͉ amyloid-enhancing factor ͉ protein aggregation ͉ rheumatoid arthritis ͉ transmissibility A myloid protein A amyloidosis (AA) occurs in patients with rheumatoid arthritis and other chronic inflammatory diseases and results from a sustained elevation of the apolipoprotein serum amyloid A (SAA) protein produced by hepatocytes under regulation by interleukin (IL)-1, IL-6, and tumor necrosis factor (1). This acute-phase reactant is cleaved into an Ϸ76-residue N-terminal fragment deposited as amyloid predominately in the kidneys, liver, and spleen. The disorder also can be induced experimentally in susceptible strains of mice by inflammatory stimuli that result in an Ͼ1,000-fold increase in SAA concentration (2). Further, the lag phase of this process is greatly decreased by injecting or feeding animals extracts of amyloidladen spleens of affected mice (2-5).To determine whether amyloid-containing food products exhibit amyloid enhancing factor (AEF) activity, we used a more robust in vivo murine model of AA amyloidosis involving mice carrying the human IL-6 (hIL-6) gene under control of either the murine metallothionein-1 (MT-1) (MT-1/hIL-6) or histocompatibility H2-L d (H2/hIL-6) promoter (6). Typically, AA amyloid develops in these animals at Ϸ5 mo of age and is initially located predominately in the perifollicular regions of the spleen. Over the next 2-3 mo, the deposits spread rapidly into the liver parenchyma, renal glomerular and intertubular regions, cardiac muscle, tongue, and gastrointestinal tract and lead to death at Ϸ8-9 mo. However, by injection into 8-wk-old transgenic mice of a ...

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Induction of AApoAII amyloidosis by various heterogeneous amyloid fibrils

Cited by 39 publications

References 27 publications

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2)

Induction of cerebral β-amyloidosis: Intracerebral versus systemic Aβ inoculation

Amyloidogenic potential of foie gras

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