Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models

Yan Yang, Nicholas H. Varvel, Bruce Lamb, Karl Herrup

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Nerve cells that re-enter a cell cycle will die rather than divide, a fact that likely underlies the neurodegeneration in Alzheimer's disease (AD). Several mouse models of familial AD have been created, and although many display amyloid plaques in their brains, none captures the extensive pattern of nerve cell death found in the human disease. Using both immunocytochemistry and fluorescent in situ hybridization, we show that neurons in three different mouse models reproduce the ectopic cell cycling found in human AD. The temporal and spatial appearance of the cell cycle events in the mouse closely mimics the human disease progression. The cell-cycle events are evident 6 months before the first amyloid deposits and significantly precede the appearance of the first CD45+ microglia. These data suggest that the ectopic initiation of cell-cycle processes in neurons is an early sign of neuronal distress in both human and mouse AD. The close phenotypic correspondence indicates a previously unsuspected level of fidelity of the mouse model to the human disease. Finally, the relative timing suggests that neither the activated microglia nor the amyloid plaques themselves are necessary to initiate the pathogenic events in AD.

Original languageEnglish (US)
Pages (from-to)775-784
Number of pages10
JournalJournal of Neuroscience
Volume26
Issue number3
DOIs
StatePublished - Jan 18 2006
Externally publishedYes

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Amyloid beta-Protein Precursor
Transgenic Mice
Cell Cycle
Alzheimer Disease
Amyloid Plaques
Neurons
Microglia
Fluorescence In Situ Hybridization
Disease Progression
Cell Death
Immunohistochemistry
Brain

Keywords

  • β-amyloid
  • APP
  • Cyclin A
  • FISH
  • Neuronal death
  • PCNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models. / Yang, Yan; Varvel, Nicholas H.; Lamb, Bruce; Herrup, Karl.

In: Journal of Neuroscience, Vol. 26, No. 3, 18.01.2006, p. 775-784.

Research output: Contribution to journalArticle

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