P1–032: A systems genetic approach to understand late‐onset Alzheimer's disease in mice

Background: Oxidative damage in Alzheimer disease (AD) is strongly associated with amyloid-b (Ab), a pathological hallmark of the disorder. As treatment and prevention options for dementia reach the forefront of the neuro-medical community, the benefits of antioxidant therapy are becoming increasingly evident. Sulforaphane (SFN), well-known antioxidants, found in broccoli and other cruciferous vegetables, is one of the most biologically active phytochemicals in the human diet. We hypothesized that the antioxidative activity of SFN would help protect the AD brain from brain damages induced by Ab and have significant potency as an AD therapeutic candidate. Administration of SFN ameliorated cognitive function of Ab-induced AD acute mouse models in Y-maze and passive avoidance behavior tests. Interestingly, we found that the therapeutic effect of SFN did not involve inhibition of Ab aggregation. While the exact mechanism of interaction of SFN in AD has not yet been ascertained, our results suggest that SFN can aid in cognitive impairment and may protect the brain from amyloidogenic damages. Methods: 1) Transmission electron microscopy (TEM)2) Cytotoxicity test 3) Amyloidogenesis test 4) Acute AD model (male ICR, 5.5 weeks): single intracerebroventricular (i.c.v.) injection of Ab aggregates 5) Administration of SFN administration via intraperitoneal (i.p.) injection 6) Behavior tests: Y-maze and passive avoidance (PA) tests. Results: From Y-maze and PA tests, SFN significantly improved cognitive, working memory and contextual memory of acute AD model increasing alternation and latency (Figure A). However, the ThT assay and TEM imaging indicated that SFN did not directly interact with Ab in its neuroprotective action (Figure B). Rather, we expect that SFN acted as a downstream protectant against Ab-induced oxidative stress in the AD brain. Conclusions: Administration of SFN ameliorated cognitive dysfunction ofAb-inducedADacutemice.Since aggregationofAb is oneof the principle causes of neuronal dysfunction in the disorder, therapeutic strategies for AD have focused on development of Ab modulators affecting on abnormal production and accumulation of Ab. Although SFN did not regulate amyloidogenesis, the downstream protective role was noteworthy against Ab-induced oxidative stress. Thus, we suggest that antioxidants such as SFN can be a complementary but promising strategy to approach AD treatment.