Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice

• Main Authors: Elena M. Ribé, Mar Pérez, Berta Puig, Ignasi Gich, Filip Lim, Mar Cuadrado, Teresa Sesma, Silvia Catena, Belén Sánchez, María Nieto, Pilar Gómez-Ramos, M.Asunción Morán, Felipe Cabodevilla, Lluis Samaranch, Lourdes Ortiz, Alberto Pérez, Isidro Ferrer, Jesús Avila, Teresa Gómez-Isla
• Format: Article
• Language: English
• Published: Elsevier 2005-12-01
• Series: Neurobiology of Disease
• Subjects: APP; β-amyloid; Tau; Lysosomes; Stereology; Neuronal loss
• Online Access: http://www.sciencedirect.com/science/article/pii/S096999610500152X

Even though the idea that amyloid β peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein processing and tau alterations in this type of dementia remains controversial. We further investigated the role of β-amyloid production/deposition in tau pathology and neuronal cell death in the mouse brain by crossing Tg2576 and VLW lines expressing human mutant amyloid precursor protein and human mutant tau, respectively. The resulting double transgenic mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain limbic areas. These findings challenge the idea that tau pathology in Alzheimer's disease is merely a downstream effect of amyloid production/deposition and suggest that reciprocal interactions between β-amyloid and tau alterations may take place in vivo.