title: Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice.
abstract: BACKGROUND
  Illuminating the role of the microtubule-associated protein tau in neurodegenerative diseases is of increasing importance, supported by recent studies establishing novel functions of tau in synaptic signalling and cytoskeletal organization. In severe dementias like Alzheimer's disease (AD), synaptic failure and cognitive decline correlate best with the grade of tau-pathology. To address synaptic alterations in tauopathies, we analyzed the effects of mutant tau expression on excitatory postsynapses in vivo.
  
  
  RESULTS
  Here we followed the fate of single dendritic spines in the neocortex of a tauopathy mouse model, expressing human P301S mutated tau, for a period of two weeks. We observed a continuous decrease in spine density during disease progression, which we could ascribe to a diminished fraction of gained spines. Remaining spines were enlarged and elongated, thus providing evidence for morphological reorganization in compensation for synaptic dysfunction. Remarkably, loss of dendritic spines in cortical pyramidal neurons occurred in the absence of neurofibrillary tangles (NFTs). Therefore, we consider prefibrillar tau species as causative for the observed impairment in spine plasticity.
  
  
  CONCLUSIONS
  Dendritic spine plasticity and morphology are altered in layer V cortical neurons of P301S tau transgenic mice in vivo. This does not coincide with the detection of hyperphosphorylated tau in dendritic spines.
authors.forename: Nadine A
authors.initials: NA
authors.lastname: Hoffmann
authors.forename: Mario M
authors.initials: MM
authors.lastname: Dorostkar
authors.forename: Sonja
authors.initials: S
authors.lastname: Blumenstock
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.affiliation: Department of Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. jochen.herms@dzne.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D049229:Dendritic Spines / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009154:Mutation; D009473:Neuronal Plasticity / Q000502:physiology*; D017966:Pyramidal Cells / Q000473:pathology / Q000503:physiopathology; D024801:Tauopathies / Q000235:genetics / Q000503:physiopathology*; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins