Amyloid-beta (A beta) aggregation, tau hyperphosphorylation, oxidative stress, and neuroinflammation are major pathophysiological events in Alzheimer's disease (AD). However, the relationships among these processes and which first exerts an effect are unknown. In the present study, we investigated age-dependent behavioral changes and the sequential pathological progression from the brain to the periphery in AD transgenic (PS1(V97L)-Tg) mice and their wild-type littermates. We discovered that the brain A beta significantly increased at 6 months old, the increased brain A beta caused memory dysfunction, and the ability of A beta to induce tau hyperphosphorylation might be due to oxidative stress and neuroinflammatory reactions. The levels of A beta(42), total tau (t-tau), oxidative stress parameters, and proinflammatory cytokines in plasma can be used to differentiate between PS1(V97L)-Tg mice and their wild-type littermates at different time points. Collectively, our findings support the hypothesis that A beta is a trigger among these pathophysiological processions and show that plasma biomarkers can reflect the condition of the AD brain.