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. 2016 May 30;53(3):773-85.
doi: 10.3233/JAD-160280.

Outstanding Phenotypic Differences in the Profile of Amyloid-β between Tg2576 and APPswe/PS1dE9 Transgenic Mouse Models of Alzheimer's Disease

José Antonio Allué, Leticia Sarasa, María Izco, Virginia Pérez-Grijalba, Noelia Fandos, María Pascual-Lucas, Samuel Ogueta, Pedro Pesini, Manuel Sarasa
Free PMC article

Outstanding Phenotypic Differences in the Profile of Amyloid-β between Tg2576 and APPswe/PS1dE9 Transgenic Mouse Models of Alzheimer's Disease

José Antonio Allué et al. J Alzheimers Dis. .
Free PMC article

Abstract

APPswe/PS1dE9 and Tg2576 are very common transgenic mouse models of Alzheimer's disease (AD), used in many laboratories as tools to research the mechanistic process leading to the disease. In order to augment our knowledge about the amyloid-β (Aβ) isoforms present in both transgenic mouse models, we have developed two chromatographic methods, one acidic and the other basic, for the characterization of the Aβ species produced in the brains of the two transgenic mouse models. After immunoprecipitation and micro-liquid chromatography-electrospray ionization mass spectrometry/mass spectrometry, 10 species of Aβ, surprisingly all of human origin, were detected in the brain of Tg2576 mouse, whereas 39 species, of both murine and human origin, were detected in the brain of the APP/PS1 mouse. To the best of our knowledge, this is the first study showing the identification of such a high number of Aβ species in the brain of the APP/PS1 transgenic mouse, whereas, in contrast, a much lower number of Aβ species were identified in the Tg2576 mouse. Therefore, this study brings to light a relevant phenotypic difference between these two popular mice models of AD.

Keywords: Alzheimer’s disease; MALDI-TOF/TOF; Micro-LC-ESI-Q-TOF; amyloid peptide; immunoprecipitation; transgenic mouse models.

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Figures

Fig.1
Fig.1
Mass spectrum of a brain extract from Tg2576 mice (aged 18 months) after immunoprecipitation with 1F3.
Fig.2
Fig.2
XIC of the Aβ peptides detected by Micro LC-ESI-MS/MS in a brain extract from Tg2576 mice (aged 18 months).
Fig.3
Fig.3
Mass spectrum of a brain extract from APP/PS1 mice (aged 18 months) after immunoprecipitation with mAb 4G8. Full spectral range (A); low-mid mass range (B); high mass range (C).
Fig.4
Fig.4
XIC of some of the largest Aβ peptides detected by Micro LC-ESI-MS/MS in brain extract from APP/PS1 mice (aged 18 months).
Fig.5
Fig.5
XIC of some of the truncated Aβ peptides detected by Micro LC-ESI-MS/MS in brain extract from APP/PS1 mice (aged 18 months).
Fig.6
Fig.6
XIC of some of the endogenous Aβ peptides detected by Micro LC-ESI-MS/MS in brain extract from APP/PS1 mice (aged 18 months).
See this image and copyright information in PMC

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