Zhang_2014_PLoS.One_9_e85885

Transgenic mouse models are powerful tools in exploring the mechanisms of AD. Most current transgenic models of AD mimic the memory impairment and the main pathologic features, among which the formation of beta-amyloid (Abeta) plaques is considered a dominant pathologic event. Recently, Abeta oligomers have been identified as more neurotoxic than Abeta plaques. However, no ideal transgenic mouse model directly support Abeta oligomers as a neurotoxic species due to the puzzling effects of amyloid plaques in the more widely-used models. Here, we constructed a single-mutant transgenic (Tg) model harboring the PS1V97L mutation and used Non-Tg littermates as a control group. Employing the Morris water maze, electrophysiology, immunohistochemistry, biochemistry, and electron microscopy, we investigated behavioral changes and pathology progression in our single-mutant transgenic model. We discovered the pathological alteration of intraneuronal accumulation of Abeta oligomers without Abeta plaques in the PS1V97L-Tg mouse model, which might be the result of PS1 gene mutation. Following Abeta oligomers, we detected synaptic alteration, tau hyperphosphorylation and glial activation. This model supports an initial role for Abeta oligomers in the onset of AD and suggests that Abeta plaques may not be the only prerequisite. This model provides a useful tool for studying the role of Abeta oligomers in AD pathogenesis.