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 (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage ma...

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Bibliographic Details
Published in:	Experimental neurology 2015-05, Vol.267, p.219-229
Main Authors:	Collins, Jessica M., King, Anna E., Woodhouse, Adele, Kirkcaldie, Matthew T.K., Vickers, James C.
Format:	Article
Language:	eng
Subjects:	Age Factors Alzheimer Disease - complications Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer's disease Amyloid beta-Peptides - metabolism Amyloid beta-Protein Precursor - genetics Animals APP/PS1 Beta-amyloid Brain Injuries - etiology Brain Injuries - genetics Brain injury Calcium-Binding Proteins - metabolism Disease Models, Animal Encephalitis - etiology Encephalitis - genetics Gene Expression Regulation - genetics Humans Macrophages - pathology Mice Mice, Inbred C57BL Mice, Transgenic Microfilament Proteins - metabolism Microglia Microglia - pathology Nerve Tissue Proteins - metabolism Plaque, Amyloid - etiology Plaque, Amyloid - genetics Presenilin-1 - genetics Synapses Synapses - metabolism Synapses - pathology Time Factors
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Summary:	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 (Aβ) 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 Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE, 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 24h and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24h or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ 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 24h PI or 7d PI. There was a significant (p0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24h PI (compared to sites distant to the injury and the corresponding area in sham mice; p0.05). 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 Aβ 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 Aβ plaque pathology that causes synaptic degeneration. •Focal brain injury did not affect Aβ plaque deposition in APP/PS1 mice.•The microglial/macrophage response to injury was the same in Wt and APP/PS1 mice.•The astrocytic response to injury was the same in Wt and APP/PS1 mice.•Both Wt and APP/PS1 mice recover lost synaptophysin immunoreactivity post-injury.
ISSN:	0014-4886 1090-2430