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Modulated expressions in behavior and APP processing in transgenic mice overexpressing NSE-controlled APPsw
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Abstracts: Clinical Assessment / 1 (Suppl 1) (2005)
break this bottleneck for research and discovery. Methods: Telemakus, a knowledge base creation system, is being utilized to develop a knowledge resource to support research on biomarkers in AD. Extracted research findings with links to the full-text data tables and figures and relevant genomics information are displayed in a consistent format that promotes rapid literature review an drilling down for more specific information. Further an interactive visualization interface provides graphical displays of research inter-relationships from documents across a domain allowing the user to review previously reported research connections and, develop hypotheses for future research. Conclusions: With innovative approach to presentation of research findings the Telemakus knowledge base system offers scientists new strategies to support knowledge discovery in the biomarkers and AD research domain. P-023
DYSREGULATION OF CELL CYCLE REGULATING PROTEINS IN PERIPHERAL LYMPHOCYTES IN THE PATIENTS WITH ALZHEIMER’S DISEASE
Doh Kwan Kim1, Hyeran Kim2, Young Ah Kwon3, Sung Ho Chung2; 1 Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Samsung Medical Center, Seoul, Republic of Korea; 3Samsung Biomedical Research Institute, Seoul, Republic of Korea Background: Extensive neuronal death occurring in the Alzheimer’s disease (AD) may be related with the apoptosis. Recent studies have suggested that regulatory failure of cell cycle appeared to be very early event of AD pathogenesis in neuronal cells as well as in peripheral lymphocytes. Objective(s): We compared the change of cyclin dependent kinases (CDKs), which is related with G1/S phase transition in the cell cycle, between AD patients and normal controls using peripheral lymphocytes. Methods: We obtained CDKs from peripheral lymphocytes of 37 AD patients and 18 age-matched normal subjects. Cells in first culture were considered to be G-zero (G0) cells. We measured CDK2, CDK4, and CDK6 at baseline (T0). Thereafter, we observed CDKs 24 hours later after using PHA (phytohemaglutinin) (N24). Meanwhile, we observed CDKs 24 hours later again with rapamycin treatment (T24). Results: At baseline (T0), CDK2 and CDK6 were increased in AD patients compared to the control group (p⬍0.001, p⫽0.038, respectively). CDK2 was increased in AD patients more than control group after using PHA (T24, p⫽0.007). After rapamycin treatment for 24 hours (N24), CDK2, CDK4, and CDK6 were increased in the patients compared to the controls (p⫽0.002, p⫽0.022, p⫽0.011, respectively). Conclusions: This results showed that the cell cycle regulating proteins in AD patients, which are related with G1/S phase transition, were increased in peripheral lymphocytes compared to those in normal controls. P-024
MODULATED EXPRESSIONS IN BEHAVIOR AND APP PROCESSING IN TRANSGENIC MICE OVEREXPRESSING NSE-CONTROLLED APPSW
Jaeho Oh, Jungsik Cho, Sunbo Shim, Daeyoun Hwang, Seungwan Jee, Suhae Lee, JunSeo Goo, Sujin Seo, Yongkyu Kim; National Institute of Toxicological Research, Korea FDA, Seoul, Republic of Korea Background: Nicastrin is a component of the presenilin (PS) protein complex involved in ␥-secretase. Objective: The aim in the study is to examine how the over-expression of the wild type human nicastrin (hNCTw) and mutant human nicastrin (hNCTm, D336A/Y337A) regulate the brain function and APP processing. Methods: hNCTw and hNCTm were microinjected into mouse fertilize embryo and produced transgenic mice respectively. Conclusion: A behavioral dysfunction was shown at 10 months of age. Also, significant reductions were observed, and as a consequence, the C-terminus of C99-APP were shown to be more increased in transgenic mice than non-transgenic littermates. In addition, both levels of A-42 and ␥-secretase activity were increased in both transgenic mice
compared with their non-transgenic littermates. Thus, overexpression of hNCTw or hNCTm in transgenic mice might be able to assemble into the active ␥-secretase complex capable of processing of APP, which is associated with a modulate in behaviors. In parallel, NCT is a novel target for the development of therapeutic treatments.
SUNDAY, JUNE 19, 2005 CLINICAL ASSESSMENT P-025—P-056 P-025
FACIALS EMOTIONS AND POSITIVE DIAGNOSIS OF ALZHEIMER’S DISEASE WITH (M.A.R.I.E.) METHOD OF ANALYSIS AND RESEARCH OF THE EMOTION INTEGRATION
Granato Philippe1, Bruyer Raymond2, Van Gansberghe Jean - Pierre3; 1 Centre Hospitalier de valenciennes, Valenciennes, France; 2Cognitive Neuroscience research unit, University of Louvain-la-Neuve, Louvain-laNeuve, Belgium; 3Mathematician, Bruxelles, Belgium Objective: The hippocampus is involved in the memory and the integration of emotions. The goal of this work is to investigate an impairment of the visual perception of facial emotions (VPFE) of subjects having contracted the Alzheimer’s disease (AD). The expected benefit is a positive infra-clinical diagnosis of AD allowing early medicinal treatment. Design: To compare PVFE of aged subjects having contracted AD with the mentally healthy (i.e. without dementia) aged subjects. Materials and Methods: We use the Method of Analysis and Research of the Emotion Integration (M.A.R.I.E.) witch allows accurate quantification of the visual perception of facial emotions (VPFE). We compare results of the CONTROL group to the ones of the AD group : (NINCDS. ADRDA). The CONTROLgroup includes 15 men and 15 women; aged 68⫹/-1,5 MMS average 30; Mattis average 140; no previous or current somatic or psychiatric pathologies. The MA group includes 21 women and 12 men aged 73,1⫹/-8,5 MMSES 25,5⫹/-2,9 MATISS 126,8⫹/-9,5. Dispaying 1 face stimulus, we studied the emotional sets: anger-fear, anger-sadness, joysadness, neutral (N)-anger; N-disgust; N-joy; N-fear; N-surprise; N-sadness. Results: The VPFE is seriously impaired by the AD. These subjects perceive the whole set of emotions with great difficulty. Globally, categorical perception ends up as a merre linear perception. Fear, surprise and sadness are perceived wrongly. Disgust and joy are better perceived. Confusion between anger and fear is significant. Perception of anger, disgust, and joy is still categorical but at the cost of disappearing sensitivity. The perceptive emotional quotient (PEQ) collapses. Conclusion: This work confirms the dysfunction of the VPFE brought about by the AD and forces us to adapt our relational approach to people with this disease. The major impact on fear perception may confirm the impairment of the amygdalo-hippocampal complex in case of AD. The concomitant occurence of an amnesic disorder and an emotional disorder would reinforce the probability of an organic impairment of the hippocampus and therefore of the highly likely occurence of neuro-fibrillary degeneration. The angerfear emotional set would be the most detrimental development for persons with the AD. Therefore a positive infra clinic diagnosic of the AD becomes feasible.
Abstracts: Clinical Assessment / 1 (Suppl 1) (2005)
break this bottleneck for research and discovery. Methods: Telemakus, a knowledge base creation system, is being utilized to develop a knowledge resource to support research on biomarkers in AD. Extracted research findings with links to the full-text data tables and figures and relevant genomics information are displayed in a consistent format that promotes rapid literature review an drilling down for more specific information. Further an interactive visualization interface provides graphical displays of research inter-relationships from documents across a domain allowing the user to review previously reported research connections and, develop hypotheses for future research. Conclusions: With innovative approach to presentation of research findings the Telemakus knowledge base system offers scientists new strategies to support knowledge discovery in the biomarkers and AD research domain. P-023
DYSREGULATION OF CELL CYCLE REGULATING PROTEINS IN PERIPHERAL LYMPHOCYTES IN THE PATIENTS WITH ALZHEIMER’S DISEASE
Doh Kwan Kim1, Hyeran Kim2, Young Ah Kwon3, Sung Ho Chung2; 1 Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Samsung Medical Center, Seoul, Republic of Korea; 3Samsung Biomedical Research Institute, Seoul, Republic of Korea Background: Extensive neuronal death occurring in the Alzheimer’s disease (AD) may be related with the apoptosis. Recent studies have suggested that regulatory failure of cell cycle appeared to be very early event of AD pathogenesis in neuronal cells as well as in peripheral lymphocytes. Objective(s): We compared the change of cyclin dependent kinases (CDKs), which is related with G1/S phase transition in the cell cycle, between AD patients and normal controls using peripheral lymphocytes. Methods: We obtained CDKs from peripheral lymphocytes of 37 AD patients and 18 age-matched normal subjects. Cells in first culture were considered to be G-zero (G0) cells. We measured CDK2, CDK4, and CDK6 at baseline (T0). Thereafter, we observed CDKs 24 hours later after using PHA (phytohemaglutinin) (N24). Meanwhile, we observed CDKs 24 hours later again with rapamycin treatment (T24). Results: At baseline (T0), CDK2 and CDK6 were increased in AD patients compared to the control group (p⬍0.001, p⫽0.038, respectively). CDK2 was increased in AD patients more than control group after using PHA (T24, p⫽0.007). After rapamycin treatment for 24 hours (N24), CDK2, CDK4, and CDK6 were increased in the patients compared to the controls (p⫽0.002, p⫽0.022, p⫽0.011, respectively). Conclusions: This results showed that the cell cycle regulating proteins in AD patients, which are related with G1/S phase transition, were increased in peripheral lymphocytes compared to those in normal controls. P-024
MODULATED EXPRESSIONS IN BEHAVIOR AND APP PROCESSING IN TRANSGENIC MICE OVEREXPRESSING NSE-CONTROLLED APPSW
Jaeho Oh, Jungsik Cho, Sunbo Shim, Daeyoun Hwang, Seungwan Jee, Suhae Lee, JunSeo Goo, Sujin Seo, Yongkyu Kim; National Institute of Toxicological Research, Korea FDA, Seoul, Republic of Korea Background: Nicastrin is a component of the presenilin (PS) protein complex involved in ␥-secretase. Objective: The aim in the study is to examine how the over-expression of the wild type human nicastrin (hNCTw) and mutant human nicastrin (hNCTm, D336A/Y337A) regulate the brain function and APP processing. Methods: hNCTw and hNCTm were microinjected into mouse fertilize embryo and produced transgenic mice respectively. Conclusion: A behavioral dysfunction was shown at 10 months of age. Also, significant reductions were observed, and as a consequence, the C-terminus of C99-APP were shown to be more increased in transgenic mice than non-transgenic littermates. In addition, both levels of A-42 and ␥-secretase activity were increased in both transgenic mice
compared with their non-transgenic littermates. Thus, overexpression of hNCTw or hNCTm in transgenic mice might be able to assemble into the active ␥-secretase complex capable of processing of APP, which is associated with a modulate in behaviors. In parallel, NCT is a novel target for the development of therapeutic treatments.
SUNDAY, JUNE 19, 2005 CLINICAL ASSESSMENT P-025—P-056 P-025
FACIALS EMOTIONS AND POSITIVE DIAGNOSIS OF ALZHEIMER’S DISEASE WITH (M.A.R.I.E.) METHOD OF ANALYSIS AND RESEARCH OF THE EMOTION INTEGRATION
Granato Philippe1, Bruyer Raymond2, Van Gansberghe Jean - Pierre3; 1 Centre Hospitalier de valenciennes, Valenciennes, France; 2Cognitive Neuroscience research unit, University of Louvain-la-Neuve, Louvain-laNeuve, Belgium; 3Mathematician, Bruxelles, Belgium Objective: The hippocampus is involved in the memory and the integration of emotions. The goal of this work is to investigate an impairment of the visual perception of facial emotions (VPFE) of subjects having contracted the Alzheimer’s disease (AD). The expected benefit is a positive infra-clinical diagnosis of AD allowing early medicinal treatment. Design: To compare PVFE of aged subjects having contracted AD with the mentally healthy (i.e. without dementia) aged subjects. Materials and Methods: We use the Method of Analysis and Research of the Emotion Integration (M.A.R.I.E.) witch allows accurate quantification of the visual perception of facial emotions (VPFE). We compare results of the CONTROL group to the ones of the AD group : (NINCDS. ADRDA). The CONTROLgroup includes 15 men and 15 women; aged 68⫹/-1,5 MMS average 30; Mattis average 140; no previous or current somatic or psychiatric pathologies. The MA group includes 21 women and 12 men aged 73,1⫹/-8,5 MMSES 25,5⫹/-2,9 MATISS 126,8⫹/-9,5. Dispaying 1 face stimulus, we studied the emotional sets: anger-fear, anger-sadness, joysadness, neutral (N)-anger; N-disgust; N-joy; N-fear; N-surprise; N-sadness. Results: The VPFE is seriously impaired by the AD. These subjects perceive the whole set of emotions with great difficulty. Globally, categorical perception ends up as a merre linear perception. Fear, surprise and sadness are perceived wrongly. Disgust and joy are better perceived. Confusion between anger and fear is significant. Perception of anger, disgust, and joy is still categorical but at the cost of disappearing sensitivity. The perceptive emotional quotient (PEQ) collapses. Conclusion: This work confirms the dysfunction of the VPFE brought about by the AD and forces us to adapt our relational approach to people with this disease. The major impact on fear perception may confirm the impairment of the amygdalo-hippocampal complex in case of AD. The concomitant occurence of an amnesic disorder and an emotional disorder would reinforce the probability of an organic impairment of the hippocampus and therefore of the highly likely occurence of neuro-fibrillary degeneration. The angerfear emotional set would be the most detrimental development for persons with the AD. Therefore a positive infra clinic diagnosic of the AD becomes feasible.