P4–010: Cross‐inhibition of beta‐amyloid plaque formation by alpha‐synuclein

Bachhuber, Teresa; McCarter, Joanna F; Tahirović, Sabina; Nuscher, Brigitte; Kamp, Frits; Abou‐Ajram, Claudia; Serrano‐Pozo, Alberto; Hyman, Bradley T.; Haass, Christian; Meyer‐Luehmann, Melanie

doi:10.1016/j.jalz.2013.05.1398

Cited by 11 publications

(14 citation statements)

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“…Thus, several studies have examined the fate of neurogenesis in AD and in transgenic mouse models of AD, all of which provided inconclusive and contradictory results (Jin et al , ,b; Zhang et al , ; Ermini et al , ; Demars et al , ; Moon et al , ; Ekonomou et al , ). In an attempt to link amyloid pathology specifically to alterations in adult neurogenesis, we performed intra‐hippocampal injections of Aβ‐containing brain extracts into 5xFAD transgenic mice that previously have been shown to robustly induce Aβ plaque formation in vivo (Kane et al , ; Meyer‐Luehmann et al , ; Bachhuber et al , ). Most recently published studies focused on the identification of the seed‐inducing factor (Langer et al , ; Hamaguchi et al , ; Fritschi et al , ,b).…”

Section: Introductionmentioning

confidence: 99%

Seed‐induced Aβ deposition is modulated by microglia under environmental enrichment in a mouse model of Alzheimer's disease

et al. 2017

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Alzheimer's disease (AD) is characterized by severe neuronal loss as well as the accumulation of amyloid‐β (Aβ), which ultimately leads to plaque formation. Although there is now a general agreement that the aggregation of Aβ can be initiated by prion‐like seeding, the impact and functional consequences of induced Aβ deposits (Aβ seeding) on neurons still remain open questions. Here, we find that Aβ seeding, representing early stages of plaque formation, leads to a dramatic decrease in proliferation and neurogenesis in two APP transgenic mouse models. We further demonstrate that neuronal cell death occurs primarily in the vicinity of induced Aβ deposits culminating in electrophysiological abnormalities. Notably, environmental enrichment and voluntary exercise not only revives adult neurogenesis and reverses memory deficits but, most importantly, prevents Aβ seeding by activated, phagocytic microglia cells. Our work expands the current knowledge regarding Aβ seeding and the consequences thereof and attributes microglia an important role in diminishing Aβ seeding by environmental enrichment.

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Section: Introductionmentioning

confidence: 99%

Seed‐induced Aβ deposition is modulated by microglia under environmental enrichment in a mouse model of Alzheimer's disease

et al. 2017

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“…; Bachhuber et al . ). In vitro data indicated that subtoxic concentrations of Aβ1‐42 induce the significant increase in intra‐ and extra‐cellular ASN levels in neuronal cells, as well as promote ASN aggregation in a cell‐free system (Masliah et al .…”

Section: Does Cdk5 Promote Association Between Misfolded Proteins Commentioning

confidence: 97%

“…Previously it has been hypothesized that Ab and ASN mutually affect their accumulation and toxicity (Kallhoff et al 2007;Kazmierczak et al 2008;Bachhuber et al 2015). In vitro data indicated that subtoxic concentrations of Ab1-42 induce the significant increase in intra-and extracellular ASN levels in neuronal cells, as well as promote ASN aggregation in a cell-free system (Masliah et al 2001;Majd et al 2013).…”

Section: Does Cdk5 Promote Association Between Misfolded Proteins Commentioning

confidence: 99%

Cdk5 at crossroads of protein oligomerization in neurodegenerative diseases: facts and hypotheses

Wilkaniec

Czapski

Adamczyk

2015

Journal of Neurochemistry

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Cyclin-dependent kinase 5 (Cdk5) is involved in proper neurodevelopment and brain function and serves as a switch between neuronal survival and death. Overactivation of Cdk5 is associated with many neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. It is believed that in those diseases Cdk5 may be an important link between disease-initiating factors and cell death effectors. A common hallmark of neurodegenerative disorders is incorrect folding of specific proteins, thus leading to their intra-and extracellular accumulation in the nervous system. Abnormal Cdk5 signaling contributes to dysfunction of individual proteins and has a substantial role in either direct or indirect interactions of proteins common to, and critical in, different neurodegenerative diseases. While the roles of Cdk5 in a-synuclein (ASN) -tau or b-amyloid peptide (Ab) -tau interactions are well documented, its contribution to many other pertinent interactions, such as that of ASN with Ab, or interactions of the Ab -ASN -tau triad with prion proteins, did not get beyond plausible hypotheses and remains to be proven. Understanding of the exact position of Cdk5 in the deleterious feedforward loop critical for development and progression of neurodegenerative diseases may help designing successful therapeutic strategies of several fatal neurodegenerative diseases.

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“…Les données in vivo sont plus contradictoires. Certaines études suggèrent que des phénomènes d'hétéronucléation pourraient intervenir entre Ab et Tau (Gotz et al 2001;Bolmont et al 2007;Vasconcelos et al 2016) mais pourraient également limiter les processus de nucléation (Bachhuber et al 2015). Bien que cette hypothèse soit intéressante, elle doit encore être démontrée in vivo.…”

Section: Risques D'ensemencement Par Des Hétéronucléantsunclassified

Transmission des lésions amyloïdes de la maladie d’Alzheimer : apports des modèles animaux

Gary¹,

Comoy²,

Dhénain³

2017

bavf

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Depuis la découverte du caractère transmissible des maladies à prions, d'autres protéinopathies cérébrales ont été soupçonnées d'être similairement transmissibles. La maladie d'Alzheimer (MA) est caractérisée par des dépôts cérébraux de peptides b-amyloïdes (Ab) et de protéines Tau hyperphosphorylées, respectivement en plaques amyloïdes et dégénérescences neurofibrillaires. Bien qu'aucune étude épidémiologique ne montre que la MA se transmette entre individus, plusieurs études ont récemment soulevé des soupçons de transmission iatrogène des dépôts b-amyloïdes chez l'Homme. Elles suggèrent que le changement de conformation (ou mépliement) de l'Ab et son agrégation se produit par des mécanismes de nucléation-élongation et de propagation, similaires à ceux décrits pour les maladies à prions. Ici, nous présentons une revue de la littérature démontrant à partir d'études in vivo la pertinence des mécanismes de mépliement et agrégation de type prion pour la pathologie b-amyloïde.

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P4–010: Cross‐inhibition of beta‐amyloid plaque formation by alpha‐synuclein

Cited by 11 publications

References 0 publications

Seed‐induced Aβ deposition is modulated by microglia under environmental enrichment in a mouse model of Alzheimer's disease

Seed‐induced Aβ deposition is modulated by microglia under environmental enrichment in a mouse model of Alzheimer's disease

Cdk5 at crossroads of protein oligomerization in neurodegenerative diseases: facts and hypotheses

Transmission des lésions amyloïdes de la maladie d’Alzheimer : apports des modèles animaux

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