PT573. The effects of intestinal endotoxemia on APP, PS1 and BACE expression in Alzheimer’s disease

s | 11 and path of small molecule. FITC-dextran (4kDa) was injected into cortices of young, aged, and AD mice. Centering the injection site, circle mask was divided into eight pieces, which were classified into artery or vein-dominant based on vessel distribution. We compare the intensity and decline rates of FITC signal at each piece of the mask. The discrepancy transforms into the uniformity index (UI) and ΔAAC The UI was higher in cortex than simple diffusion. The ΔAAC was higher in the artery-dominant piece. FITC-dextran moves into artery pieces faster than vein pieces and the difference is assumed to reflect the amount of PVD. In aged and AD mice, the UIs are relatively steady and the ΔAAC is significantly decreased compared with normal mouse. These results indicate that PVD is impaired in AD. PT572 Advances in the Development of Tau PET Radiotracers and Their Clinical Applications Kazuhiko Yanai 1, Ryuichi Harada 1 and Nobuyuki Okamura 1, 2 1 Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan 2 Department of Pharmacology, Tohoku Medical and Pharmaceutical University, Sendai, Japan Abstract Objective: Recent progress in the development of tau-selective PET tracers enabled non-invasive visualization of neurofibrillary pathology in the human brain. The amount and spatial distribution of tau tracer binding in the brain is closely associated with neurodegeneration and cognitive symptom of dementia. Therefore, tau PET imaging is expected to be useful for tracking disease progression, assessing disease severity, and accurately predicting dementia prognosis. The purpose of this study was to assess the clinical usefulness of THK tau PET tracers. Methods: Subjects with Alzheimer’s disease, mild cognitive impairment and healthy controls (Number of each group is more than 10) underwent [18F]THK-5351 and [11C]PiB PET scans. Standard uptake value ratios between 50–60 minutes post injection for THK-5351 was calculated using the cerebellar cortex as a reference region. Results: Subjects with mild cognitive impairment showed higher THK retention in the fusiform gyrus, inferior temporal and parietal cortices than healthy control subjects. Patients with Alzheimer’s disease showed higher and more extensive neocor-Objective: Recent progress in the development of tau-selective PET tracers enabled non-invasive visualization of neurofibrillary pathology in the human brain. The amount and spatial distribution of tau tracer binding in the brain is closely associated with neurodegeneration and cognitive symptom of dementia. Therefore, tau PET imaging is expected to be useful for tracking disease progression, assessing disease severity, and accurately predicting dementia prognosis. The purpose of this study was to assess the clinical usefulness of THK tau PET tracers. Methods: Subjects with Alzheimer’s disease, mild cognitive impairment and healthy controls (Number of each group is more than 10) underwent [18F]THK-5351 and [11C]PiB PET scans. Standard uptake value ratios between 50–60 minutes post injection for THK-5351 was calculated using the cerebellar cortex as a reference region. Results: Subjects with mild cognitive impairment showed higher THK retention in the fusiform gyrus, inferior temporal and parietal cortices than healthy control subjects. Patients with Alzheimer’s disease showed higher and more extensive neocortical THK retention than subjects with mild cognitive impairment. In some cognitively normal individuals, THK retention was mildly elevated in the inferior temporal area. THK retention in the parahippocampal and fusiform gyrus, inferior temporal and parietal cortices was correlated with clinical severity of dementia. Conclusion: THK-5351 enables sensitive and selective detection of neurofibrillar pathology in Alzheimer’s disease. Tau PET imaging with this tracer could be employed to study longitudinal tau deposition in normal aging and pathological process of Alzheimer’s disease. PT573 The effects of intestinal endotoxemia on APP, PS1 and BACE expression in Alzheimer’s disease Bai Han1, Hejun Li1, Xizheng Shan2, Qin Sun2, Fan Wu1 Kezhan Liu3, Litao Ma2 1Shanxi Medical University, China, 2The General Hospital of The Chinese Armed Police Forces (CAPF) China, 3The Shanxi Provincial Children’s Hospital, China Abstract Objective: Early our animal experiments study showed that AD rats occurs intestinal endotoxemia (IETM), and with the increasing of endotoxin, the APP, PS1, BACE mRNA increased and promote the generation of Aβ. The aim of this study was to observe the occurance of IETM in AD patients and to investigate the effect of intestinal endotoximia in AD, provide evidence for the prevention and treatment of AD. Methods According to the inclusion and the exclusion criteria, choose AD patients and healthy eldly, evaluate cognition by the Mini mental state examination (MMSE) and Alzheimer’s disease assessment scale cognitive subscale (ADAS-cog), detect the serum LPS, TNF-α and Aβ level by ELISA, detect APP, PS1 and BACE mRNA expression by real-time PCR. All the data were analyzed by SPSS 17.0. Results 1. The AD group and the control group showed no significant differences in sex (χ2=0.312, P=0.576), age (t=0.243, P=0.809) and education level (u=735.000, P=0.682). 2. The MMSE score of AD group was significantly lower than the control group (u=0.000, P<0.001), the ADAS-cog score was significantly higher than that in control group (u=0.000, P<0.001), the differences were statistically significant. 3. The LPS (u=0.000, P<0.001), TNF-α (t=6.175, P<0.001), Aβ (u=13.000, P<0.001) levels were significantly higher than the control group, the differences were statistically significant. 4. The APP (u=16.000, P<0.001), PS1 (u=24.000, P<0.001) and BACE (u=60.000, P<0.001) mRNA expression levels in AD group were significantly higher than the control group, the differences were statistically significant. 5. The LPS level was highly related to the Aβ level (r=0.894), The LPS level was moderately related to the APP (r=0.563), BACE (r=0.486) mRNA expression. The correlation between LPS level and PS1 mRNA expression was not significant. Conclusion: This study preliminary confirmed that AD patients occurs IETM, and IETM could upregulate the expression of APP, the key enzyme BACE by induce inflammatory cytokines, and then promote Aβ generation, lead to the development of AD.