Early Increases in Soluble Amyloid-β Levels Coincide with Cholinergic Degeneration in 3xTg-AD Mice

Article type: Short Communication

Authors: Girão da Cruz, M. Teresa^{a; 1} | Jordão, Jessica^{a; b} | DaSilva, Kevin A.^{a; b; c} | Ayala-Grosso, Carlos A.^{a; 2} | Ypsilanti, Athéna^{a; b; 3} | Weng, Ying-Qi^a | LaFerla, Frank M.^d | McLaurin, JoAnne^{b; c} | Aubert, Isabelle^{a; b; *}

Affiliations: [a] Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Biological Sciences, Brain Sciences, Toronto, ON, Canada | [b] Faculty of Medicine, Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada | [c] Centre for Research in Neurodegenerative Diseases, University of Toronto, ON, Canada | [d] Department of Neurobiology and Behavior, University of California Irvine, CA, USA

Correspondence: [*] Correspondence to: Isabelle Aubert, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Biological Sciences, Brain Sciences, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. E-mail: [email protected].

Note: [1] Present address: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

Note: [2] Present address: Laboratory of Cellular and Molecular Pathology, Center for Experimental Medicine, Instituto Venezolano de Investigaciones Científicas, IVIC, Venezuela.

Note: [3] Present address: Institut de la Vision, Département Biologie du Développement, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR S968, Université Pierre et Marie Curie (UPMC) Paris IV, UMR S968, Centre National de la Recherche Scientifique (CNRS) UMR 7210, F-75012 Paris, France.

Abstract: Accumulation of amyloid-β peptides (Aβ) and cholinergic degeneration are hallmarks of Alzheimer's disease (AD). In a triple transgenic mouse model of AD (3xTg-AD), soluble Aβ42 levels were detected in the septum by 2 months of age, reaching their highest levels at 3–6 months and decreasing at 12 months. Deficits in the number of septal cholinergic neurons and the length of hippocampal cholinergic axons were observed starting at 4 months in 3xTg-AD mice. Our results show that septal Aβ and septohippocampal cholinergic pathology in 3xTg-AD mice occur at an early stage of disease.

Keywords: Amyloid-β peptides, choline acetyltransferase, cholinergic neurons, gamma-aminobutyric acid, medial septal nucleus

DOI: 10.3233/JAD-2012-100732

Journal: Journal of Alzheimer's Disease, vol. 32, no. 2, pp. 267-272, 2012