Advertisement
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

    X
  • Raphael Zinn,

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

    X
  • 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

    X
  • Lyndsey M. Konen,

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

    X
  • 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

    X
  • Richard P. Tan,

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

    X
  • Ian A. Clark,

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

    X
  • Andrea Abdipranoto,

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

    X
  • 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

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

Reader Comments (6)

Post a new comment on this article

Publisher's Note: Corrections to Minor Typographical Errors in the Article

Posted by PLoS_ONE_Group on 03 May 2013 at 18:27 GMT

The Abstract contains two typographical errors. The correct Abstract is the following:

Recent human trials of treatments for Alzheimer’s disease (AD) have been largely unsuccessful, raising the idea that treatment may need to be started earlier in the disease, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whether amyloid-β (Aβ) plaque load may serve this purpose. We investigated this in the hAPP-J20 AD mouse model by studying disease pathology at 6, 12, 24 and 36 weeks. Using robust stereological methods, we found there is no neuron loss in the hippocampal CA3 region at any age. However, loss of neurons from the hippocampal CA1 region begins as early as 12 weeks of age. The extent of neuron loss increases with age, correlating with the number of activated microglia. Gliosis was also present, but plateaued during aging. Increased hyperactivity and spatial memory deficits occurred at 16 and 24 weeks. Meanwhile, the appearance of plaques and oligomeric Aβ were essentially the last pathological changes, with significant changes only observed at 36 weeks of age. This is surprising given that the hAPP-J20 AD mouse model is engineered to over-expresses Aβ. Our data raises the possibility that plaque load may not be the best marker for early AD and suggests that activated microglia could be a valuable marker to track disease progression.


The following errors occur in the Body sections:

Introduction, paragraph 4, 4th sentence.
It should read "…cytokines such as tumour necrosis factor-alpha (TNF-α) and…" with a bracket instead of a question mark after "α"

Introduction, paragraph 6, 3rd sentence
"…changes occur well in advance of the formation of Aβ plaques." with a space between "Aβ" and "plaques"

Results, Aβ expression and plaque formation occurs in an age dependent manner, 3rd sentence
"Quantification of 6E10 immunoreactivity revealed a significant increase in total Aβ levels with age" with a space between "Aβ" and "levels"

Discussion, Paragraph 3, last sentence
"…Either by Aβ or by other mechanisms is a key…" with a space between "Aβ" and "or"

Discussion, paragraph 6, 7th sentence
"In addition, 11C-PK11195-labelled activated microglia…" Please put a comma after "addition"

Disscussion, paragraph 7, 6th sentence
"…correlation between activated microglia, Aβ and neuronal cell loss…" with a space between "Aβ" and "and"


The following error occurs in the References:

Reference number 12 has been incorrectly formatted. The correct reference is:
12. Brun A, Englund E (1981) Regional pattern of degeneration in Alzheimer’s disease: neuronal loss and histopathological grading. Histopathology 5: 549–564. <Find this article online>

Each reference after number 12 is one less than what is stated in the list. For example, reference number 14 is actually reference number 13. All of the in-text citations will refer to the renumbered reference list.

No competing interests declared.