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 (A beta) plaques is considered a dominant pathologic event. Recently, A beta oligomers have been identified as more neurotoxic than A beta plaques. However, no ideal transgenic mouse model directly support A beta 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 PS1(V97L) 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 A beta oligomers without A beta plaques in the PS1(V97L)-Tg mouse model, which might be the result of PS1 gene mutation. Following A beta oligomers, we detected synaptic alteration, tau hyperphosphorylation and glial activation. This model supports an initial role for A beta oligomers in the onset of AD and suggests that A beta plaques may not be the only prerequisite. This model provides a useful tool for studying the role of A beta oligomers in AD pathogenesis.