Amyloid neuropathology in the single Arctic APP transgenic model affects interconnected brain regions

Rönnbäck, Annica; Sagelius, Hanna; Bergstedt, Karin Dillner; Näslund, Jan; Westermark, Gunilla T.; Winblad, Bengt; Graff, Caroline

doi:10.1016/j.neurobiolaging.2011.07.012

Cited by 41 publications

(43 citation statements)

References 43 publications

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“…3) (Ye et al 2015b). A similar systematic emergence of endogenous Ab lesions has been reported in an APP-transgenic mouse model expressing Arctic mutant Ab (Rönnbäck et al 2012).…”

Section: Trafficking Of Ab Seeds Trafficking Within the Brainsupporting

confidence: 70%

The Prion-Like Properties of Amyloid-β Assemblies: Implications for Alzheimer's Disease

Walker

Schelle

Jucker

2016

Cold Spring Harb Perspect Med

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“…3) (Ye et al 2015b). A similar systematic emergence of endogenous Ab lesions has been reported in an APP-transgenic mouse model expressing Arctic mutant Ab (Rönnbäck et al 2012).…”

Section: Trafficking Of Ab Seeds Trafficking Within the Brainsupporting

confidence: 70%

The Prion-Like Properties of Amyloid-β Assemblies: Implications for Alzheimer's Disease

Walker

Schelle

Jucker

2016

Cold Spring Harb Perspect Med

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“…The APP Arc mice display subtle cognitive decline, whereas the APP Swe/Lon mice show a more aggressive disease progression. Also, the localization of the neuropathological alterations is different between the two models: in the APP Arc mice, the lesions are mainly detected in the subiculum, which is in contrast to APP Swe/Lon mice, where Aβ deposits are spread throughout the neocortex (30).…”

Section: σ1r and Pacs-2 Knockdown Causes Degeneration Of Hippocampalmentioning

confidence: 93%

Modulation of the endoplasmic reticulum–mitochondria interface in Alzheimer’s disease and related models

Hedskog

Pinho

Filadi

et al. 2013

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

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408

367

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It is well-established that subcompartments of endoplasmic reticulum (ER) are in physical contact with the mitochondria. These lipid raft-like regions of ER are referred to as mitochondria-associated ER membranes (MAMs), and they play an important role in, for example, lipid synthesis, calcium homeostasis, and apoptotic signaling. Perturbation of MAM function has previously been suggested in Alzheimer's disease (AD) as shown in fibroblasts from AD patients and a neuroblastoma cell line containing familial presenilin-2 AD mutation. The effect of AD pathogenesis on the ER-mitochondria interplay in the brain has so far remained unknown. Here, we studied ERmitochondria contacts in human AD brain and related AD mouse and neuronal cell models. We found uniform distribution of MAM in neurons. Phosphofurin acidic cluster sorting protein-2 and σ1 receptor, two MAM-associated proteins, were shown to be essential for neuronal survival, because siRNA knockdown resulted in degeneration. Up-regulated MAM-associated proteins were found in the AD brain and amyloid precursor protein (APP) Swe/Lon mouse model, in which up-regulation was observed before the appearance of plaques. By studying an ER-mitochondria bridging complex, inositol-1,4,5-triphosphate receptor-voltage-dependent anion channel, we revealed that nanomolar concentrations of amyloid β-peptide increased inositol-1,4,5-triphosphate receptor and voltage-dependent anion channel protein expression and elevated the number of ER-mitochondria contact points and mitochondrial calcium concentrations. Our data suggest an important role of ER-mitochondria contacts and cross-talk in AD pathology.AD mouse models | hippocampal neurons | human cortical brain tissue

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“…In humans [120] as in animals (for example, in APParc tg mice [104]), phases of progression of amyloid deposits have been described: localized deposits, made of insoluble (possibly misfolded) Aβ, affect an ever-increasing number of regions of the brain. The aggregation propensity of Aβ peptides may influence the distribution of the deposits: Aβ40, being less aggregation prone than Aβ42, may reach the vessels whereas Aβ42 more readily aggregates in the parenchyma [53,54].…”

Section: Is There a Toxic Form Of Aβ?mentioning

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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Amyloid neuropathology in the single Arctic APP transgenic model affects interconnected brain regions

Cited by 41 publications

References 43 publications

The Prion-Like Properties of Amyloid-β Assemblies: Implications for Alzheimer's Disease

The Prion-Like Properties of Amyloid-β Assemblies: Implications for Alzheimer's Disease

Modulation of the endoplasmic reticulum–mitochondria interface in Alzheimer’s disease and related models

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

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