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Research Article

Neuroinflammation and Neuronal Loss Precede Aβ Plaque Deposition in the hAPP-J20 Mouse Model of Alzheimer’s Disease

  • Amanda L. Wright,

    Affiliations: Neurodegenerative Disorders, Garvan Institute of Medical Research, Neuroscience Department, Sydney, Australia, Faculty of Medicine, University of New South Wales, Sydney, Australia

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  • Raphael Zinn,

    Affiliations: Neurodegenerative Disorders, Garvan Institute of Medical Research, Neuroscience Department, Sydney, Australia, Faculty of Medicine, University of New South Wales, Sydney, Australia

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  • Barbara Hohensinn,

    Affiliations: Neurodegenerative Disorders, Garvan Institute of Medical Research, Neuroscience Department, Sydney, Australia, Faculty of Medicine, University of New South Wales, Sydney, Australia

    Current address: Institute of Molecular Biosciences, University of Graz, Graz, Austria

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  • Lyndsey M. Konen,

    Affiliation: Neurodegenerative Disorders, Garvan Institute of Medical Research, Neuroscience Department, Sydney, Australia

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  • Sarah B. Beynon,

    Affiliation: Neurodegenerative Disorders, Garvan Institute of Medical Research, Neuroscience Department, Sydney, Australia

    Current address: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia

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  • Richard P. Tan,

    Affiliation: Neurodegenerative Disorders, Garvan Institute of Medical Research, Neuroscience Department, Sydney, Australia

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  • Ian A. Clark,

    Affiliation: Research School of Biology, Australian National University, Canberra, Australia

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  • Andrea Abdipranoto,

    Affiliation: Neurodegenerative Disorders, Garvan Institute of Medical Research, Neuroscience Department, Sydney, Australia

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  • Bryce Vissel mail

    b.vissel@garvan.org.au

    Affiliations: Neurodegenerative Disorders, Garvan Institute of Medical Research, Neuroscience Department, Sydney, Australia, Faculty of Medicine, University of New South Wales, Sydney, Australia

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  • Published: April 01, 2013
  • DOI: 10.1371/journal.pone.0059586

Reader Comments (6)

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The findings don't reflect what has been found in humans

Posted by robcw on 04 Apr 2013 at 22:42 GMT

http://www.thelancet.com/...(13)70044-9/fulltext
In this long term Australian study in humans Ab changes occurred many years before cognitive and hippocampal volume and neuronal loss occurred. Is good to see Australia leading the way in this research. The article regarding this study by Clifford Fram, AAP National Medical Writer From: AAP April 03, 2013
http://www.news.com.au/br... did not make it clear that this was a study in mice or that it differed from human studies.

No competing interests declared.

RE: The findings don't reflect what has been found in humans

bvissel replied to robcw on 09 Apr 2013 at 23:59 GMT

Response from Amanda Wright and Bryce Vissel:

Thank you for your comment. There is currently a great debate amongst the scientific community as to the relevance of imaging plaques in AD for early diagnosis (for an excellent discussion see http://www.alzforum.org/n...). The recent paper published in Lancet (http://www.thelancet.com/...(13)70044-9) is an outstanding study showing accumulation of amyloid beta in AD. However, it does not elucidate if amyloid beta is the best marker for early AD. Interestingly, recent studies investigating inflammatory markers in humans have also shown that microglia correlates strongly to MMSE, more so than plaque load. Our study also shows that in this mouse model, disease progress correlates with inflammation. By accurately quantifying inflammatory and neuronal cell numbers overtime, our study has been able to show age progressive decline in an APP mouse model prior to plaque formation. Our study has shown that neuroinflammation, behavioural decline and neuronal cell loss occurs in an APP expressing model before the formation of amyloid plaque deposition. This has implications for considering if plaque is indeed the best correlate of early AD.

No competing interests declared.