Genetically augmenting tau levels does not modulate the onset or progression of Aβ pathology in transgenic mice

Salvatore Oddo, Antonella Caccamo, David Cheng, Bahareh Jouleh, Reidun Torp, Frank M. LaFerla

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The two hallmark pathologies of Alzheimer's disease (AD) are amyloid plaques, composed of the small amyloid-β (Aβ) peptide, and neurofibrillary tangles, comprised aggregates of the microtubule binding protein, tau. The molecular linkage between these two lesions, however, remains unknown. Based on human and mouse studies, it is clear that the development of Aβ pathology can trigger tau pathology, either directly or indirectly. However, it remains to be established if the interaction between Aβ and tau is bidirectional and whether the modulation of tau will influence Aβ pathology. To address this question, we used the 3xTg-AD mouse model, which is characterized by the age-dependent buildup of both plaques and tangles. Here we show that genetically augmenting tau levels and hyperphosphorylation in the 3xTg-AD mice has no effect on the onset and progression of Aβ pathology. These data suggest that the link between Aβ and tau is predominantly if not exclusively unidirectional, which is consistent with the Aβ cascade hypothesis and may explain why tauopathy-only disorders are devoid of any Aβ pathology.

Original languageEnglish (US)
Pages (from-to)1053-1063
Number of pages11
JournalJournal of Neurochemistry
Volume102
Issue number4
DOIs
StatePublished - Aug 2007
Externally publishedYes

Fingerprint

Pathology
Transgenic Mice
Alzheimer Disease
Amyloid
Tauopathies
Microtubule Proteins
Neurofibrillary Tangles
Amyloid Plaques
Carrier Proteins
Modulation
Peptides

Keywords

  • Aging
  • Alzheimer's disease
  • Amyloid-β oligomers
  • Neurofibrillary tangles
  • Plaques

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Genetically augmenting tau levels does not modulate the onset or progression of Aβ pathology in transgenic mice. / Oddo, Salvatore; Caccamo, Antonella; Cheng, David; Jouleh, Bahareh; Torp, Reidun; LaFerla, Frank M.

In: Journal of Neurochemistry, Vol. 102, No. 4, 08.2007, p. 1053-1063.

Research output: Contribution to journalArticle

Oddo, Salvatore ; Caccamo, Antonella ; Cheng, David ; Jouleh, Bahareh ; Torp, Reidun ; LaFerla, Frank M. / Genetically augmenting tau levels does not modulate the onset or progression of Aβ pathology in transgenic mice. In: Journal of Neurochemistry. 2007 ; Vol. 102, No. 4. pp. 1053-1063.
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