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Acta Neuropathol Commun. 2015 Nov 14;3:72. doi: 10.1186/s40478-015-0252-9.

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

Xu G1,2,3,4, Ran Y1,4, Fromholt SE1,3,4, Fu C5, Yachnis AT6, Golde TE1,2,4, Borchelt DR7,8,9,10.

Author information

1
Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.
2
McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.
3
SantaFe HealthCare Alzheimer's Disease Research Center, University of Florida, Gainesville, FL, 32610, USA.
4
Department of Neuroscience, University of Florida, 1275 Center Dr., Box 100159, Gainesville, FL, 32610, USA.
5
Department of Medicine, University of Florida, Gainesville, FL, 32610, USA.
6
Department of Pathology, University of Florida College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
7
Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA. drb1@ufl.edu.
8
McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA. drb1@ufl.edu.
9
SantaFe HealthCare Alzheimer's Disease Research Center, University of Florida, Gainesville, FL, 32610, USA. drb1@ufl.edu.
10
Department of Neuroscience, University of Florida, 1275 Center Dr., Box 100159, Gainesville, FL, 32610, USA. drb1@ufl.edu.

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 mice developing extracellular compact, cored, neuritic deposits that primarily localize to white matter tracts and meningial 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.

PMID:
26566997
PMCID:
PMC4644287
DOI:
10.1186/s40478-015-0252-9
[Indexed for MEDLINE]
Free PMC Article

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