Tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of Alzheimer's disease-relevant tau constructs in organotypic hippocampal slices
Autor(en): | Shahani, Neelam Subramaniam, Srinivasa Wolf, Tobias Tackenberg, Christian Brandt, Roland |
Affiliationen: | Department of Neurobiology, University of Osnabrück, 49076 Osnabrück, Germany. neelam.shahani@biologie.uni-osnabrueck.de | Erscheinungsdatum: | 2006 | Journal: | The Journal of neuroscience : the official journal of the Society for Neuroscience | Volumen: | 26 | Ausgabe: | 22 | Startseite: | 6103 | Seitenende: | 6114 | Zusammenfassung: | Alzheimer's disease (AD) is characterized by progressive loss of neurons in selected brain regions, extracellular accumulations of amyloid beta, and intracellular fibrils containing hyperphosphorylated tau. Tau mutations in familial tauopathies confirmed a central role of tau pathology; however, the role of tau alteration and the sequence of tau-dependent neurodegeneration in AD remain elusive. Using Sindbis virus-mediated expression of AD-relevant tau constructs in hippocampal slices, we show that disease-like tau modifications affect tau phosphorylation at selected sites, induce Alz50/MC1-reactive pathological tau conformation, cause accumulation of insoluble tau, and induce region-specific neurodegeneration. Live imaging demonstrates that tau-dependent degeneration is associated with the development of a "ballooned" phenotype, a distinct feature of cell death. Spine density and morphology is not altered as judged from algorithm-based evaluation of dendritic spines, suggesting that synaptic integrity is remarkably stable against tau-dependent degeneration. The data provide evidence that tau-induced cell death involves apoptotic as well as nonapoptotic mechanisms. Furthermore, they demonstrate that targeted expression of tau in hippocampal slices provides a novel model to analyze tau modification and spatiotemporal dynamics of tau-dependent neurodegeneration in an authentic CNS environment. |
DOI: | 10.1523/JNEUROSCI.4245-05.2006 | Externe URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675219 |
Zur Langanzeige
Seitenaufrufe
2
Letzte Woche
0
0
Letzter Monat
2
2
geprüft am 10.05.2024