The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease

Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (A beta) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of A beta plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APP(SWE), PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24 h and 7 d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-A beta antibody) MOAB-2-labeled plaques at either 24 h or 7 d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical A beta plaques but focal injury had no statistically significant (p > 0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24 h PI or 7 d PI. There was a significant (p < 0.001) increase in cross-sectional cortical area occupied by lba-1 positive microglia in injured mice compared to sham animals, however this response did not differ between APP/PS1 and Wt mice (p > 0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24 h PI (compared to sites distant to the injury and the corresponding area in sham mice; p < 0.01), but not after 7 d PI (p > 0.05). There was no significant effect of genotype on this response (p > 0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter A beta plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of A beta plaque pathology that causes synaptic degeneration. (C) 2015 Elsevier Inc. All rights reserved.