Multiple events lead to dendritic spine loss in triple transgenic Alzheimer's disease mice

Bittner, Tobias; Fuhrmann, Martin; Burgold, Steffen; Ochs, Simon M.; Hoffmann, Nadine; Mitteregger, Gerda; Kretzschmar, Hans; LaFerla, Frank M. und Herms, Jochen (2010): Multiple events lead to dendritic spine loss in triple transgenic Alzheimer's disease mice.
In: PLOS ONE 5(11), e15477

Abstract

The pathology of Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) peptide, hyperphosphorylated tau protein, neuronal death, and synaptic loss. By means of long-term two-photon in vivo imaging and confocal imaging, we characterized the spatio-temporal pattern of dendritic spine loss for the first time in 3xTg-AD mice. These mice exhibit an early loss of layer III neurons at 4 months of age, at a time when only soluble Aβ is abundant. Later on, dendritic spines are lost around amyloid plaques once they appear at 13 months of age. At the same age, we observed spine loss also in areas apart from amyloid plaques. This plaque independent spine loss manifests exclusively at dystrophic dendrites that accumulate both soluble Aβ and hyperphosphorylated tau intracellularly. Collectively, our data shows that three spatio-temporally independent events contribute to a net loss of dendritic spines. These events coincided either with the occurrence of intracellular soluble or extracellular fibrillar Aβ alone, or the combination of intracellular soluble Aβ and hyperphosphorylated tau.

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 223276
• EU-Projekte: 7. Forschungsrahmenprogramm (FP7)
• Publikationsform: Publisher's Version
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1932-6203
• Bemerkung: This work was supported by grants to JH from the Deutsche Forschungsgemeinschaft (SFB 596, A13), the Bavarian State Ministry for Science, Research and Arts (ForNeuroCell), the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, 01GZ0713, 13N10644), the German Federal Ministry of Economics and Technology (Bundesministerium für Wirtschaft und Technologie, 16IN0675), and the European Union (Neuro.GSK3, FP-7-223276).
• Sprache: Englisch