Blocking Aβ42 accumulation delays the onset and progression of tau pathology via the C terminus of heat shock protein70-interacting protein

A mechanistic link between Aβ and tau pathology

Salvatore Oddo, Antonella Caccamo, Bert Tseng, David Cheng, Vitaly Vasilevko, David H. Cribbs, Frank M. LaFerla

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

The molecular alterations that induce tau pathology in Alzheimer disease (AD) are not known, particularly whether this is an amyloid-β (Aβ)-dependent or -independent event. We addressed this issue in the 3xTg-AD mice using both genetic and immunological approaches and show that a selective decrease in Aβ42 markedly delays the progression of tau pathology. The mechanism underlying this effect involves alterations in the levels of C terminus of heat shock protein70-interacting protein (CHIP) as we show that Aβ accumulation decreases CHIP expression and increases tau levels. We show that the Aβ-induced effects on tau were rescued by restoring CHIP levels. Our findings have profound clinical implications as they indicate that preventing Aβ accumulation will significantly alter AD progression. These data highlight the critical role CHIP plays as a link between Aβ and tau and identify CHIP as a new potential target not only for AD but for other neurodegenerative disorders characterized by tau accumulation.

Original languageEnglish (US)
Pages (from-to)12163-12175
Number of pages13
JournalJournal of Neuroscience
Volume28
Issue number47
DOIs
StatePublished - Nov 19 2008
Externally publishedYes

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Staphylococcal Protein A
Shock
Alzheimer Disease
Hot Temperature
Pathology
Amyloid
Neurodegenerative Diseases
Disease Progression
Proteins

Keywords

  • Aging
  • Alzheimer's disease
  • Plaques
  • Tangles
  • Transgenic

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Blocking Aβ42 accumulation delays the onset and progression of tau pathology via the C terminus of heat shock protein70-interacting protein : A mechanistic link between Aβ and tau pathology. / Oddo, Salvatore; Caccamo, Antonella; Tseng, Bert; Cheng, David; Vasilevko, Vitaly; Cribbs, David H.; LaFerla, Frank M.

In: Journal of Neuroscience, Vol. 28, No. 47, 19.11.2008, p. 12163-12175.

Research output: Contribution to journalArticle

Oddo, Salvatore ; Caccamo, Antonella ; Tseng, Bert ; Cheng, David ; Vasilevko, Vitaly ; Cribbs, David H. ; LaFerla, Frank M. / Blocking Aβ42 accumulation delays the onset and progression of tau pathology via the C terminus of heat shock protein70-interacting protein : A mechanistic link between Aβ and tau pathology. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 47. pp. 12163-12175.
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