Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20
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-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. We found that total hippocampal Aβ expression increased with age and that plaques and oligomeric Aβ 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.
|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 00:00:00|