It has been reported that damage to the mitochondria affects the progression of Alzheimer&rsquo / s disease (AD), and that mitochondrial dysfunction is improved by omega-3. However, no animal or cell model studies have confirmed whether omega-3 inhibits AD pathology related to mitochondria deficits. In this study, we aimed to (1) identify mitigating effects of endogenous omega-3 on mitochondrial deficits and AD pathology induced by amyloid beta (A&beta / ) in fat-1 mice, a transgenic omega-3 polyunsaturated fatty acids (PUFAs)-producing animal / (2) identify if docosahexaenoic acid (DHA) improves mitochondrial deficits induced by A&beta / in HT22 cells / and (3) verify improvement effects of DHA administration on mitochondrial deficits and AD pathology in B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax (5XFAD), a transgenic A&beta / -overexpressing model. We found that omega-3 PUFAs significantly improved A&beta / -induced mitochondrial pathology in fat-1 mice. In addition, our in vitro and in vivo findings demonstrate that DHA attenuated AD-associated pathologies, such as mitochondrial impairment, A&beta / accumulation, neuroinflammation, neuronal loss, and impairment of adult hippocampal neurogenesis.