Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease

Salvatore Oddo, Antonella Caccamo, Masashi Kitazawa, Bertrand P. Tseng, Frank M. LaFerla

Research output: Contribution to journalArticle

627 Citations (Scopus)

Abstract

Amyloid-β (Aβ) containing plaques and tau-laden neurofibrillary tangles are the defining neuropathological features of Alzheimer's disease (AD). To better mimic this neuropathology, we generated a novel triple transgenic model of AD (3xTg-AD) harboring three mutant genes: β-amyloid precursor protein (βAPPSwe), presenilin-1 (PS1M146V), and tauP301L. The 3xTg-AD mice progressively develop Aβ and tau pathology, with a temporal- and regional-specific profile that closely mimics their development in the human AD brain. We find that Aβ deposits initiate in the cortex and progress to the hippocampus with aging, whereas tau pathology is first apparent in the hippocampus and then progresses to the cortex. Despite equivalent overexpression of the human βAPP and human tau transgenes, Aβ deposition develops prior to the tangle pathology, consistent with the amyloid cascade hypothesis. As these 3xTg-AD mice phenocopy critical aspects of AD neuropathology, this model will be useful in pre-clinical intervention trials, particularly because the efficacy of anti-AD compounds in mitigating the neurodegenerative effects mediated by both signature lesions can be evaluated.

Original languageEnglish (US)
Pages (from-to)1063-1070
Number of pages8
JournalNeurobiology of Aging
Volume24
Issue number8
DOIs
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Amyloid
Alzheimer Disease
Pathology
Hippocampus
Presenilin-1
Neurofibrillary Tangles
Amyloid beta-Protein Precursor
Human Development
Transgenes
Clinical Trials
Brain
Genes

Keywords

  • β-Amyloid
  • Amyloid
  • Presenilin
  • Tangles
  • Tau
  • Transgenic

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease. / Oddo, Salvatore; Caccamo, Antonella; Kitazawa, Masashi; Tseng, Bertrand P.; LaFerla, Frank M.

In: Neurobiology of Aging, Vol. 24, No. 8, 12.2003, p. 1063-1070.

Research output: Contribution to journalArticle

Oddo, Salvatore ; Caccamo, Antonella ; Kitazawa, Masashi ; Tseng, Bertrand P. ; LaFerla, Frank M. / Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease. In: Neurobiology of Aging. 2003 ; Vol. 24, No. 8. pp. 1063-1070.
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