Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease

Melanie Meyer-Luehmann, Tara L. Spires-Jones, Claudia Prada, Monica Garcia-Alloza, Alix de Calignon, Anete Rozkalne, Jessica Koenigsknecht-Talboo, David M. Holtzman, Brian J. Bacskai and Bradley T. Hyman ()
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Melanie Meyer-Luehmann: Alzheimer’s Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Tara L. Spires-Jones: Alzheimer’s Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Claudia Prada: Alzheimer’s Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Monica Garcia-Alloza: Alzheimer’s Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Alix de Calignon: Alzheimer’s Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Anete Rozkalne: Alzheimer’s Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Jessica Koenigsknecht-Talboo: Washington University School of Medicine, St Louis, Missouri 63110, USA
David M. Holtzman: Washington University School of Medicine, St Louis, Missouri 63110, USA
Brian J. Bacskai: Alzheimer’s Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Bradley T. Hyman: Alzheimer’s Disease Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA

Nature, 2008, vol. 451, issue 7179, 720-724

Abstract: Senile plaques: toxic combination The senile plaques in brains of Alzheimer's disease sufferers are thought to develop gradually over years. The involvement of plaques in the pathology of Alzheimer's disease is a hotly debated issue. New work, using mutiphoton microscopy to follow plaque formation in vivo in a mouse model of the disease, supports the view that amyloid plaques appear before local neurotoxicity is visible. Surprisingly, senile plaques form rapidly, within 24 hours: within a day or two microglial cells accumulate and neuritic abnormalities start to appear. Based on these observations, it's possible to speculate that the slow degeneration in Alzheimer's disease is marked by sudden changes in cortical structure, and that altering the kinetics of this process might change the rate of disease progression.

Date: 2008
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DOI: 10.1038/nature06616

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