Transmission of Systemic AA Amyloidosis in Animals

Murakami, Tomoaki; Ishiguro, Naotaka; Higuchi, Kenichi

doi:10.1177/0300985813511128

Cited by 77 publications

(84 citation statements)

References 74 publications

(111 reference statements)

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“…It does not imply a transmission between organisms (in the sense of level 4). However, this possibility is currently being discussed at least for Amyloid A (AA) amyloidosis in cheetahs, since systemic AA amyloidosis has been transmitted between cheetahs by ingested excrements [91]. Recent neuropathological data from iatrogenic CJD in recipients of growth hormones (GH) isolated from cadaver pituitary glands (CGH) raise the possibility of an interindividual transmission of cerebral Aβ amyloidosis (in the sense of level 4 above) under exceptional circumstances [66].…”

Section: Prions Prion-like Proteins and Propagonsmentioning

confidence: 99%

Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies

Eisele

Duyckaerts

2015

Acta Neuropathol

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In brains of patients with Alzheimer's disease (AD), Aβ peptides accumulate in parenchyma and, almost invariably, also in the vascular walls. Although Aβ aggregation is, by definition, present in AD, its impact is only incompletely understood. It occurs in a stereotypical spatiotemporal distribution within neuronal networks in the course of the disease. This suggests a role for synaptic connections in propagating Aβ pathology, and possibly of axonal transport in an antero- or retrograde way-although, there is also evidence for passive, extracellular diffusion. Striking, in AD, is the conjunction of tau and Aβ pathology. Tau pathology in the cell body of neurons precedes Aβ deposition in their synaptic endings in several circuits such as the entorhino-dentate, cortico-striatal or subiculo-mammillary connections. However, genetic evidence suggests that Aβ accumulation is the first step in AD pathogenesis. To model the complexity and consequences of Aβ aggregation in vivo, various transgenic (tg) rodents have been generated. In rodents tg for the human Aβ precursor protein, focal injections of preformed Aβ aggregates can induce Aβ deposits in the vicinity of the injection site, and over time in more distant regions of the brain. This suggests that Aβ shares with α-synuclein, tau and other proteins the property to misfold and aggregate homotypic molecules. We propose to group those proteins under the term "propagons". Propagons may lack the infectivity of prions. We review findings from neuropathological examinations of human brains in different stages of AD and from studies in rodent models of Aβ aggregation and discuss putative mechanisms underlying the initiation and spread of Aβ pathology.

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Section: Prions Prion-like Proteins and Propagonsmentioning

confidence: 99%

Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies

Eisele

Duyckaerts

2015

Acta Neuropathol

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“…Supporting this view, the only other case of a PMD shown to be naturally transmissible between individuals is amyloid-A amyloidosis in captive cheetahs (Zhang et al 2008). A similar transmission of amyloid-A amyloidosis has also been suggested to cause an epidemic of avian amyloidosis (Murakami et al 2014). There are no epidemiological studies that specifically consider whether T2D could be transmissible from individual to individual.…”

Section: Prion-like Transmission Of Protein Aggregates In "Real Life"mentioning

confidence: 89%

Prion-Like Protein Aggregates and Type 2 Diabetes

Mukherjee

Soto

2017

Cold Spring Harb Perspect Med

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Type 2 diabetes (T2D) is a highly prevalent metabolic disease characterized by chronic insulin resistance and b-cell dysfunction and loss, leading to impaired insulin release and hyperglycemia. Although the mechanism responsible for b-cell dysfunction and death is not completely understood, recent findings suggest that the accumulation of misfolded aggregates of the islet amyloid polypeptide (IAPP) in the islets of Langerhans may play an important role in pancreatic damage. Misfolding and aggregation of diverse proteins and their accumulation as amyloid in different organs is the hallmark feature in a group of chronic, degenerative diseases termed protein misfolding disorders (PMDs). PMDs include highly prevalent human illnesses such as Alzheimer's and Parkinson's disease, as well as more than 25 rarer disorders. Among them, prion diseases are unique because the pathology can be transmitted by a proteinaceous infectious agent, termed a prion, which induces disease by propagating protein misfolding and aggregation. This phenomenon has a striking resemblance to the process of protein misfolding and aggregation in all of the PMDs, suggesting that misfolded aggregates have an intrinsic potential to be transmissible. Indeed, recent studies have shown that the pathological hallmarks of various PMDs can be induced in vivo under experimental conditions by inoculating tissue extracts containing protein aggregates into animal models. In this review, we describe our current understanding of the molecular mechanism underlying the prion-like transmission of protein aggregates and its possible role in T2D.

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“…Amyloid A (AA) amyloidosis involves the pathological deposition of insoluble AA fibrils in various body tissues and organs [1,2]. Precursor protein of AA amyloidosis is serum amyloid A (SAA), which is an acute phase reactant primarily produced by hepatocytes [3].…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, there is a realistic possibility of being exposed to and acquiring AA fibrils from other species (heterologous seeding), because animal organs are consumed as food [1,9]. Uptake of heterologous AA fibrils under certain inflammatory conditions may lead to amyloidosis transmission [10][11][12].…”

Section: Introductionmentioning

confidence: 99%