Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old App(NL/NL) Knock-In Mice

Commonly used Alzheimer’s disease mouse models are based on the ectopic overexpression of the human amyloid precursor protein (APP) gene, together with a mutant presenilin gene. Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (App(NL)), failed to develop amyl...

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Autores principales: Salas, Isabel H., Callaerts-Vegh, Zsuzsanna, D’Hooge, Rudi, Saido, Takaomi C., Dotti, Carlos G., De Strooper, Bart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2018
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218137/
https://www.ncbi.nlm.nih.gov/pubmed/30320577
http://dx.doi.org/10.3233/JAD-180410
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author Salas, Isabel H.
Callaerts-Vegh, Zsuzsanna
D’Hooge, Rudi
Saido, Takaomi C.
Dotti, Carlos G.
De Strooper, Bart
author_facet Salas, Isabel H.
Callaerts-Vegh, Zsuzsanna
D’Hooge, Rudi
Saido, Takaomi C.
Dotti, Carlos G.
De Strooper, Bart
author_sort Salas, Isabel H.
collection PubMed
description Commonly used Alzheimer’s disease mouse models are based on the ectopic overexpression of the human amyloid precursor protein (APP) gene, together with a mutant presenilin gene. Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (App(NL)), failed to develop amyloid plaque aggregation or cognitive deficits. Here we characterized the effect of this mutation in more advanced ages. We show that 24-month-old App(NL/NL) mice, despite presenting an age dependent increase in insoluble amyloid-β oligomers in the prefrontal cortex, they do not develop amyloid plaque deposition, reactive gliosis, or cognitive deficits.
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spelling pubmed-62181372018-11-07 Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old App(NL/NL) Knock-In Mice Salas, Isabel H. Callaerts-Vegh, Zsuzsanna D’Hooge, Rudi Saido, Takaomi C. Dotti, Carlos G. De Strooper, Bart J Alzheimers Dis Research Article Commonly used Alzheimer’s disease mouse models are based on the ectopic overexpression of the human amyloid precursor protein (APP) gene, together with a mutant presenilin gene. Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (App(NL)), failed to develop amyloid plaque aggregation or cognitive deficits. Here we characterized the effect of this mutation in more advanced ages. We show that 24-month-old App(NL/NL) mice, despite presenting an age dependent increase in insoluble amyloid-β oligomers in the prefrontal cortex, they do not develop amyloid plaque deposition, reactive gliosis, or cognitive deficits. IOS Press 2018-10-30 /pmc/articles/PMC6218137/ /pubmed/30320577 http://dx.doi.org/10.3233/JAD-180410 Text en © 2018 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Salas, Isabel H.
Callaerts-Vegh, Zsuzsanna
D’Hooge, Rudi
Saido, Takaomi C.
Dotti, Carlos G.
De Strooper, Bart
Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old App(NL/NL) Knock-In Mice
title Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old App(NL/NL) Knock-In Mice
title_full Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old App(NL/NL) Knock-In Mice
title_fullStr Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old App(NL/NL) Knock-In Mice
title_full_unstemmed Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old App(NL/NL) Knock-In Mice
title_short Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old App(NL/NL) Knock-In Mice
title_sort increased insoluble amyloid-β induces negligible cognitive deficits in old app(nl/nl) knock-in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218137/
https://www.ncbi.nlm.nih.gov/pubmed/30320577
http://dx.doi.org/10.3233/JAD-180410
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