Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

Neuroinflammation and neuronal loss precede Abeta plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease


Abstract Recent human trials of Alzheimer?s disease (AD) treatments have largely failed, raising the idea that treatment may need to be started earlier in the disease process, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whether amyloid-? (A?) 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. We found that total hippocampal A? expression increased with age and that plaques and oligomeric A? expression were essentially the last pathological changes, with significant changes only observed at 36 weeks of age. By contrast, using robust stereological methods, we found that loss of neurons begins as early as 12 weeks of age in the hippocampal CA1, but not CA3 region. 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. Based on these results, we suggest that microglial activation may provide an earlier marker of AD pathology.

Type Journal
Authors Wright, A..; Raphael Zinna,b, Barbara Hohensinnc, Lyndsey M Konena, Sarah B Beynond, Richard Tana, Andrea Abdipranotoa, Bryce Vissela,b
Publisher Name PLoS One
Published Date 2013-04-01
Published Volume 8
Published Issue 4
Published Pages e59586
Status Published in-print
DOI 10.1371/journal.pone.0059586
URL link to publisher's version
OpenAccess link to author's accepted manuscript version