Assembly of filamentous tau aggregates in human neuronal cells

Li Wen Ko, Toni Rush, Naruhiko Sahara, Jay S. Kersh, Colin Easson, Michael DeTure, Wen Lang Lin, Yamicia D. Connor, Shu Hui C. Yen

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Intraneuronal deposition of microtubule-associated protein tau in filamentous aggregates constitutes a pathological hallmark of neurofibrillary degeneration that is characteristic of Alzheimer's disease (AD) and related disorders known collectively as tauopathies. Formation of such fibril inclusions, consisting of hyperphosphorylated tau in multiple isoforms, correlates with the severity of cognitive decline in AD. How neurofibrillary pathology evolves in tauopathy remains unclear at present, but availability of a cellular model with robust tau aggregation will permit experimental scrutiny of the mechanistic process leading to such neurodegeneration. Through the use of a serial transfection strategy in conjunction with a tau minigene construct, we succeeded in generating conditional transfectants of human neuronal lineage that overproduce wild-type human brain tau in isoforms 4R0N, 3R1N and 4R1N via TetOff and ecdysone inducible expression mechanisms. Such transgenic overexpression of tau in multiple isoforms facilitated the assembly of filamentous tau aggregates that exhibit immunoreactivities, physicochemical properties, and ultrastructural attributes reminiscent of those found in human tauopathies. The conditional tau transfectants thus provide us with a useful tool to elucidate the molecular and cellular events leading to neurofibrillary degeneration and a convenient means to test hypothetical mechanisms implicated in the etiopathogenesis of AD and related tauopathies.

Original languageEnglish (US)
Pages (from-to)605-622
Number of pages18
JournalJournal of Alzheimer's Disease
Volume6
Issue number6
DOIs
StatePublished - 2004

Keywords

  • Alzheimer's disease
  • conditional transfectant
  • neurofibrillary degeneration
  • tau
  • tau fibrillogenesis
  • tauopathy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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