title: Multiple events lead to dendritic spine loss in triple transgenic Alzheimer's disease mice.
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.
authors.affiliation: Center of Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bittner
authors.forename: Martin
authors.initials: M
authors.lastname: Fuhrmann
authors.forename: Steffen
authors.initials: S
authors.lastname: Burgold
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ochs
authors.forename: Nadine
authors.initials: N
authors.lastname: Hoffmann
authors.forename: Gerda
authors.initials: G
authors.lastname: Mitteregger
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
authors.forename: Frank M
authors.initials: FM
authors.lastname: LaFerla
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019943:Amino Acid Substitution; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001927:Brain Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013003:Somatosensory Cortex / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016875:tau Proteins