AβPP Accumulation and/or Intraneuronal Amyloid-β Accumulation? The 3xTg-AD Mouse Model Revisited

Article type: Research Article

Authors: Wirths, Oliver^{; *} | Dins, Annika | Bayer, Thomas A.

Affiliations: Division of Molecular Psychiatry, Georg-August-University Göttingen, University Medicine Göttingen, Göttingen, Germany

Correspondence: [*] Correspondence to: Oliver Wirths, Ph.D., Division of Molecular Psychiatry, Georg-August-University Göttingen, University Medicine Göttingen, von-Siebold-Str. 5, 37075 Göttingen, Germany. Tel.: +49 551 10290; Fax: +49 551 10291; E-mail: owirths@gwdg.de.

Abstract: The triple-transgenic Alzheimer's disease (AD) mouse model, 3xTg-AD, played an important role in supporting the intraneuronal amyloid-β (Aβ) hypothesis in AD. However, recent evidence claims that the 3xTg-AD mice accumulate amyloid-β protein precursor (AβPP) instead of Aβ within neurons. In the present report, we re-investigated the 3xTg-AD mouse model and confirmed recent findings of age-dependent AβPP accumulations. In addition, intraneuronal Aβ was detected mainly in the neocortex using conformation-specific as well as antibodies directed against Aβ neo-epitopes. In contrast to previous work, however, only minor levels of intraneuronal Aβ were detected in the CA1 region of the hippocampus in aged 3xTg-AD mice.

Keywords: Alzheimer's disease, amyloid, amyloid-β protein precursor, immunohistochemistry, intraneuronal amyloid-β, pyroglutamate amyloid-β, transgenic mice

DOI: 10.3233/JAD-2011-111529

Journal: Journal of Alzheimer's Disease, vol. 28, no. 4, pp. 897-904, 2012