Hallmark cellular pathology of Alzheimer's disease induced by mutant human tau expression in cultured Aplysia neurons

Or A. Shemesh, Micha E. Spira

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The mechanisms underlying neurodegenerative diseases are the outcome of pathological alterations of evolutionary conserved molecular and cellular cascades. For this reason, Drosophila and C. elegans serve as useful model systems to study various aspects of neurodegenerative diseases. Here, we introduce the advantageous use of cultured Aplysia neurons (which express over 100 diseaserelated gene homologs shared with mammals), as a platform to study cell biological processes underlying the generation of tauopathy. Using live confocal imaging to follow cytoskeletal elements, autophagosomes, lysosomes, anterogradely and retrogradely transported organelles, complemented with electron microscopy, we demonstrate that the expression of mutant human tau in cultured Aplysia neurons leads to the development of hallmark Alzheimer disease (AD) pathologies. These include a reduction in the number of microtubules and their redistribution, impaired organelle transport, a dramatic accumulation of macro-autophagosomes and lysosomes, compromised neurite morphology and degeneration. Our study demonstrates the accessibility of the platform for long-term live imaging and quantification of subcellular pathological cascades leading to tauopathy. Based on the present study, it is conceivable that this system can also be used to screen for reagents that alter the pathological cascades.

Original languageEnglish
Pages (from-to)209-222
Number of pages14
JournalActa Neuropathologica
Volume120
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • Alzheimer's disease
  • Aplysia
  • Autophagosomes lysosomes
  • Axoplasmic transport
  • Tauopathy

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