Antrodia camphorata is a particular and precious medicinal mushroom, and its fruiting body was found to provide more efficient protection from oxidative stress and inflammation than its mycelium because of its higher content of triterpenoids, total phenols, and so on. In the previous in vitro studies, the mycelium of A. camphorata is proven to provide strong neuroprotection in neuron cells and suggested to have the potential of protection against neurotoxicity of amyloid beta-protein (A beta) known as the risk factor toward Alzheimer's disease (AD) development. However, the in vivo study and the comparison study with the fruiting body have not yet been investigated. This study compared the effect of the fruiting body and mycelium of A. camphorata on alleviating the A beta 40-induced neurocytotoxicity in the in vitro A beta-damaged neuron cell model (PC-12 cell treated with A beta 40) and memory impairment in the in vivo AD animal model induced with a continuous brain infusion of A beta 40. In the results of in vitro and in vivo studies, the fruiting body possessed stronger anti-oxidative and anti-inflammatory abilities for inhibiting neurocytotoxicity in A beta 40-treated PC-12 cells and A beta 40 accumulation in A beta 40-infused brain than mycelium. Moreover, hyperphosphorylated tau (p-tau) protein expression, known as an important AD risk factor, was suppressed by the treatment of fruiting body rather than that of mycelium in the in vitro and in vivo studies. These comparisons supported the reasons why the fruiting body resulted in a more significant improvement effect on working memory ability than mycelium in the AD rats.