Characterization of an 'Amyloid Only' Transgenic (B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax) Mouse Model of Alzheimer's...

The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 μm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months. They were most abundant in the cerebral cortices, hippocampus, olfactory bulbs, some white matter tracts and the cerebellar molecular layer; no amyloid aggregates were found in the midbrain, brainstem or spinal cord, or in an equivalent number of brains from wild-type mice. Since the parahippocampal gyrus is severely damaged early in the clinical course of human Alzheimer's disease, amyloid aggregates were also assessed in this brain region and a similar temporal course of amyloid deposition was observed. Moreover, in this gyrus, the amount of aggregated amyloid showed no significant difference between left- and right-sided gyri. However, the polyclonal antibody detected a significantly greater amyloid burden than the monoclonal antibody at 3-10 months of age and the reverse was seen at 11-12 months of age. The pattern of amyloid deposition in the parahippocampal gyrus also resembled that found in the entire brain over time, when the latter was quantified by the colour deconvolution method, suggesting that this gyrus is a good marker for more widely distributed cerebral amyloid deposition. This neuropathological characterization will permit better use of the B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax transgenic mouse strain in future studies of Alzheimer's disease pathogenesis, prevention and treatment.