Table 1. Animal models of traumatic brain injury and amyloid pathology.

No difference in neuronal loss, cognition or motor function following injury versus wild-type controls

Decrease in total tissue levels of Aβ₄₀ but not Aβ₄₂ after injury

Suppression of injury-induced elevations in caspase-3 by administration of a pan-caspase inhibitor

Both caspase-cleaved APP and Aβ were reduced in association with improved histological outcome

Administration of simvistatin 3 h after injury resulted in decreased hippocampal Aβ levels, decreased hippocampal tissue loss and preserved synaptic integrity

Behavioural outcome also improved

Improved histological, radiological, behavioural and motor outcomes following injury versus BACE^+/+ mice

Administration of a γ-secretase inhibitor (DAPT) in non-transgenic mice also improved outcomes

Levels of Aβ₄₀ and Aβ₄₂ in tissues increased following injury, peaking at 2 h

Associated with increased hippocampal neuronal death and memory impairment

No Aβ plaques were observed up to 2 months after injury

Decrease in Aβ plaques at 5 and 8 months after injury versus uninjured PDAPP mice (who normally demonstrate abundant Aβ plaques at these time points)

Regression in Aβ plaque burden observed in the ipsilateral hippocampus of injured PDAPP mice 16 weeks after injury versus the contralateral hippocampus or uninjured PDAPP control mice

PDAPP mice expressing Apoe4 had increased Aβ deposition compared with those expressing Apoe3

Both groups displayed deposition at an age at which it is not observed in uninjured controls

Mice with Apoe4 demonstrated Aβ deposition that stained positive for thiaflavin-S in the molecular layer of the dentate gyrus

Extensive APP accumulation in damaged axons (1, 3 and 21 days following injury), and later in cortical neuropil

No accumulating Aβ observed intracellularly or in plaques

APP accumulation in damaged axons up to 2 weeks following injury

No Aβ observed at any time point intracellulary or in plaques

Axonal accumulation of APP observed from 6 h to 10 days following trauma

Aβ identified in damaged axons 12 h after injury

Although APP and Aβ were persistently found in axons for up to 10 days after injury, immunoreactivity reduced over time

No plaques observed at any time

Low levels of Aβ accumulated in axons, emerging at around 2 weeks after injury

More profound immunoreactivity demonstrated at 1 month and persisted up to 1 year

Extent of Aβ production was dependent on the maturity of the injury, but was uncoupled from the gene expression of APP

Accumulation of intra-axonal APP and Aβ observed 3–10 days following injury

Sparse, diffuse Aβ plaques observed in the grey and white matter over the same time course

First animal model to replicate human Aβ plaque pathology observed after traumatic brain injury

Aβ observed in axons, co-accumulating with APP, BACE and presenilin-1

This was observed acutely (3 days and persisted up to 6 months after injury)

Sparse Aβ plaques were observed both acutely and at 6 months following injury, but did not increase in number over this time