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Acta Neuropathologica Communications

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Open Access 01-12-2015 | Research

Murine Aβ over-production produces diffuse and compact Alzheimer-type amyloid deposits

Authors: Guilian Xu, Yong Ran, Susan E. Fromholt, Chunhua Fu, Anthony T. Yachnis, Todd E. Golde, David R. Borchelt

Published in: Acta Neuropathologica Communications | Issue 1/2015

Abstract

Introduction

Transgenic overexpression of amyloid precursor protein (APP) genes that are either entirely human in sequence or have humanized Aβ sequences can produce Alzheimer-type amyloidosis in mice, provided the transgenes also encode mutations linked to familial Alzheimer’s Disease (FAD). Although transgenic mice have been produced that overexpress wild-type mouse APP, no mice have been generated that express mouse APP with FAD mutations. Here we describe two different versions of such mice that produce amyloid deposits consisting of entirely of mouse Aβ peptides. One line of mice co-expresses mouse APP-Swedish (moAPPswe) with a human presenilin exon-9 deleted variant (PS1dE9) and another line expresses mouse APP-Swedish/Indiana (APPsi) using tetracycline-regulated vectors (tet.moAPPsi).

Results

Both lines of mice that produce mouse Aβ develop amyloid deposits, with the moAPPswe/PS1dE9 micedeveloping extracellular compact, cored, neuritic deposits that primarily localize to white matter tracts andmeningial layers, whereas the tet.moAPPsi mice developed extracellular diffuse cortical/hippocampal deposits distributed throughout the parenchyma.

Conclusions

These findings demonstrate that murine Aβ peptides have the capacity to produce amyloid deposits that are morphologically similar to deposits found in human AD provided the murine APP gene harbors mutations linked to human FAD.

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Title: Murine Aβ over-production produces diffuse and compact Alzheimer-type amyloid deposits
Authors: Guilian Xu
Yong Ran
Susan E. Fromholt
Chunhua Fu
Anthony T. Yachnis
Todd E. Golde
David R. Borchelt
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2015
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-015-0252-9

At a glance: The STEP trials

Springer Medicine

Murine Aβ over-production produces diffuse and compact Alzheimer-type amyloid deposits

Abstract

Introduction

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Results

Conclusions

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