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Journal article
Tau-dependent microtubule disassembly initiated by prefibrillar β-amyloid
The Journal of cell biology, v 175(4), pp 541-546
20 Nov 2006
PMID: 17101697
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Alzheimer's Disease (AD) is defined histopathologically by extracellular β-amyloid (Aβ) fibrils plus intraneuronal tau filaments. Studies of transgenic mice and cultured cells indicate that AD is caused by a pathological cascade in which Aβ lies upstream of tau, but the steps that connect Aβ to tau have remained undefined. We demonstrate that tau confers acute hypersensitivity of microtubules to prefibrillar, extracellular Aβ in nonneuronal cells that express transfected tau and in cultured neurons that express endogenous tau. Prefibrillar Aβ42 was active at submicromolar concentrations, several-fold below those required for equivalent effects of prefibrillar Aβ40, and microtubules were insensitive to fibrillar Aβ. The active region of tau was localized to an N-terminal domain that does not bind microtubules and is not part of the region of tau that assembles into filaments. These results suggest that a seminal cell biological event in AD pathogenesis is acute, tau-dependent loss of microtubule integrity caused by exposure of neurons to readily diffusible Aβ.
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Details
- Title
- Tau-dependent microtubule disassembly initiated by prefibrillar β-amyloid
- Creators
- Michelle E. King - University of VirginiaHo-Man Kan - Department of BiologyPeter W. Baas - Drexel UniversityAlev Erisir - Department of Psychology,Charles G. Glabe - University of California, IrvineGeorge S. Bloom - University of Virginia
- Publication Details
- The Journal of cell biology, v 175(4), pp 541-546
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000242291200004
- Scopus ID
- 2-s2.0-33751218015
- Other Identifier
- 991019167870104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology