Jang Jae Lee

Differences Between APOE Carriers and Non-APOE Carriers on Neurocognitive Tests: Jensen Effects?:

Background: Being a carrier of the apolipoprotein E (APOE) ε4 allele is a clear risk factor for development of Alzheimer’s disease (AD). On some neurocognitive tests, there are smaller differences between carriers and noncarriers, while other tests show larger differences. Aims: We explore whether the size of the difference between carriers and noncarriers is a function of how well the tests measure general intelligence, so whether there are Jensen effects. Methods: We used the method of correlated vectors on 441 Korean older adults at risk for AD and 44 with AD. Results: Correlations between APOE carriership and test scores ranged from −.05 to .11 (normal), and −.23 to .54 (AD). The differences between carriers and noncarriers were Jensen effects: r = .31 and r = .54, respectively. Conclusion: A composite neurocognitive score may show a clearer contrast between APOE carriers and noncarriers than a large number of scores of single neurocognitive tests.

APOE PROMOTER POLYMORPHISM ACTS AS AN EFFECT MODIFIER FOR APOE ε4 ON ALZHEIMER’S DISEASE

Zbigniew Wszolek, John C. van Swieten, Suzee E. Lee, University of California San Francisco, San Francisco, CA, USA; Erasmus Medical Center, Rotterdam, Netherlands; Alzheimer Center and Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands; Mayo Clinic, Rochester, MN, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; University of California, Los Angeles School of Medicine, Los Angeles, CA, USA; Massachusetts General Hospital, Boston, MA, USA; University of California Los Angeles, Los Angeles, CA, USA; Indiana University School of Medicine, Indianapolis, IN, USA; University of California San Diego, La Jolla, CA, USA; Washington University School of Medicine, St. Louis, MO, USA; Mayo Clinic, Jacksonville, FL, USA; University of British Columbia, Vancouver, BC, Canada; Gertrude H. Sergievsky Center at Columbia University, New York, NY, USA; Univ of Penn, Philadelphia, PA, USA; University of North Carolina, Chapel Hill, NC, USA; CurePSP, New York, NY, USA; National Alzheimer’s Coordinating Center, University of Washington, Seattle, WA, USA; University of California San Diego, San Diego, CA, USA; Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA; Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins University School of Medicine, Baltimore, MD, USA; University of Alabama at Birmingham, Birmingham, AL, USA; Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada; The AFTD, Radnor, PA, USA; Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Northwestern University, Chicago, IL, USA; Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands. Contact e-mail: Suzee.Lee@ucsf.edu

PURE WHITE MATTER HYPERINTENSITY DOES NOT EVOKE CORTICAL SHRINKAGE AND COGNITIVE DYSFUNCTION

P2-444 PURE WHITE MATTER HYPERINTENSITY DOES NOT EVOKE CORTICAL SHRINKAGE AND COGNITIVE DYSFUNCTION Hoowon Kim, Ilhan Choo, Kun Ho Lee, Yu Yong Choi, Jang Jae Lee, Ji Yeon Chung, Kyu Yeong Choi, Department of Neurology, Chosun University School of Medicine, Gwangju, South Korea; Chosun University/Chosun University Hospital, Gwangju, South Korea; Department of Life Science, Chosun University, Gwangju, South Korea; National Research Center for Dementia, Chosun University, Gwangju, South Korea; Department of Premedics, Chosun University, Gwangju, South Korea. Contact e-mail: hoowon@chosun.ac.kr

AGE-WEIGHTED POLYGENIC RISK MODEL EFFECTIVELY PREDICTS THE ONSET OF ALZHEIMER DISEASE

addressed this problem by developing a technology to reproducibly generate stable soluble Aß1-42 oligomers that are devoid of monomeric or fibrillar Aß and show biophysical properties indistinguishable from the native species. Furthermore, Crossbeta oligomers demonstrate typical functionality of pathological Ab species such as neurotoxicity, in vivo LTP depression and induction of inflammatory response. The availability of the stable oligomers opens previously inaccessible avenues for R&D. For example, it enabled high throughput screening of drug-like compound libraries. Derived from a 100k compound screening effort, small molecule CBB68 was identified and shown to neutralize oligomer-induced neurotoxicity in rat primary neurons and to rescue the synaptic deficit induced by Ab oligomers in vivo as well as in vitro. In particular, the in vivo LTP assay demonstrated the efficacy and brain penetration of CBB68 after intravenous administration. In another application, Crossbeta’s oligomers have also been used to select shark antibodies that specifically recognize a conformational oligomeric epitope and bind to Aß142 oligomers with high affinity (sub-nM), but not to the monomers or fibrils. This antibody provides potential to selectively quantify Aß1-42 oligomers in patient material as part of a high sensitivity biomarker assay together with the stable Crossbeta oligomers as calibrator. Furthermore, the oligomers are excellent research tools, e.g. in disease-relevant bioassays. We show and conclude that the stable oligomers enable multiple applications and constitute optimum drug targets.

NORMATIVE MODEL OF BRAIN STRUCTURES IN THE KOREAN ELDERLY: A GENERAL LINEAR APPROACH

Results:The activity of rostal ACC, right superior temporal gyrus, right insula and frontal gyrus were positively correlated with [Glx]abs during the numerical Stroop task (Figure 3). [Glx]abs was not dependent on age (mean [Glx]abs 1⁄4 16.9662.83 mM; Pearson correlation coefficient 1⁄4 -0.175; p1⁄40.225). Conclusions:This is the first study providing neurochemical explanation of the BOLD change during attention control task in healthy adults. Our novel finding of [Glx]abs significantly positively correlated with the activated region over the rostral ACC provides a neurochemical explanation of the neural activations observed in the attention control task, implying the BOLD signal change during attention control task was mediated through neurovascular coupling by Glu. As the ACC is involved in attention control and exhibits rich glutamatergic innervation [1,2], such elevation in this glutamatergic activity may then lead to the observed task-induced activation in the ACC. References: [1] Bozkurt et al., 2005,[2] Palomero-Gallagher et al., 2008 P2-402 COMPREHENSIVE MORPHOMETRIC CORTICAL/SUBCORTICAL NORMATIVE DATA: FREESURFER ATLASES COMPARISON Olivier Potvin, Louis Dieumegarde, Simon Duchesne, Institut Universitaire en Sante Mentale de Quebec, Quebec, QC, Canada; Faculty of Medicine, University Laval, Qu ebec, QC, Canada. Contact e-mail: simon.duchesne@fmed.ulaval.ca

A DATA TRANSFORMATION TECHNIQUE FOR MULTI-SCANNER MRI STUDIES: APPLICATION TO MCI PATIENT CLASSIFICATION

20-29 123 0 5 0.46 0.87 0 2 30-39 236 0 10 0.68 1.39 0 2 40-49 296 0 6 0.82 1.89 0 3 50-59 290 0 11 1.57 2.05 1 4 60-69 293 0 15 2.25 2.36 2 5 70-79 169 0 15 4.02 3.21 4 9 80-90 32 0 14 4.47 3.49 4 9 Yu Yong Choi, Balaji Kannappan, Jang Jae Lee, Kyu Yeong Choi, Hyangmi Kim, Byeong Chae Kim, Kun Ho Lee, National Research Center for Dementia, Chosun University, Gwangju, Republic of South Korea, Department of Premedics, Chosun University, Gwangju, Republic of South Korea; National Research Center for Dementia, Chosun University, Gwangju, Republic of South Korea; Department of Life Sciences, Gwangju, Republic of South Korea; National Research Center for Dementia, Gwangju, Republic of South Korea; National Research Centre for Dementia, Gwangju, Republic of South Korea; Chonnam National University Medical School, Gwangju, Republic of South Korea; Department of Life Science, Chosun University, Gwangju, Republic of South Korea. Contact e-mail: yuyongchoi@gmail.com

ASSOCIATION STUDY OF HIGH-RISK GENETIC VARIANTS WITH ALZHEIMER'S DISEASE IN THE KOREAN ELDERLY

emoire et de la Maladie d’Alzheimer (IM2A), UPMC, Paris, France; Gerontopole, Inserm U 1027, Alzheimers Disease Research and Clinical Center, Toulouse University Hospital, Toulouse, France; 11 University of Toulouse III, Toulouse, France; 12 CHU Toulouse, Toulouse, France; Inserm UMR 1027, Toulouse, France; Lille University, Lille, France; Inserm, U1219 and Bordeaux University, Bordeaux, France; 16 Bordeaux University, Bordeaux, France; 17 Memory Consultation, CHU Bordeaux, Bordeaux, France; Bordeaux University Hospital, Bordeaux, France; Hôpital de la Timone, Marseille, France; 20 Aix Marseille University, Marseille, France; 21 Hôpitaux Universitaires de Strasbourg, CMRR, Strasbourg, France; 22 ICube, University of Strasbourg, Strasbourg, France; Memory Resources and Research Center, CHRU Gui de Chauliac, Montpellier, France; Inserm-UM 1183, Montpellier, France; 25 Charpennes Hôpital-Hopitaux Civils de Lyon, Villeurbanne, France; 26 CMRR Paris Nord Ile de France, Paris, France; 27 University of Paris Diderot/AP-HP, PARIS, France; InsermU942, Paris, France; Universit e Paris Descartes, Sorbonne Paris Cit e, EA4468, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Broca, Paris, France; 31 Hôpital General, Dijon, France; 32 Centre M emoire de Ressources et de Recherche, CHU de Nice, Nice, France; CNRS, UMR 7225 ICM, Paris, France; 34 Inria, Aramis Project-Team, Centre de Recherche Paris-Rocquencourt, Paris, France; 35 Sorbonne Universites, UPMCUniv Paris 06, UMR S 1127, F-75013, Paris, France; Institut du Cerveau et de laMoelle epiniere, ICM, F-75013, Paris, France; Inserm, U1127, F-75013, Paris, France; 38 Inserm, Bordeaux, France. Contact e-mail: carole.Dufouil@isped. u-bordeaux2.fr

EFFECTS OF APOE GENE POLYMORPHISMS ON LATE ONSET ALZHEIMER’S DISEASE IN A KOREAN POPULATION

P3-083 EFFECTS OFAPOE GENE POLYMORPHISMS ON LATE ONSETALZHEIMER’S DISEASE IN A KOREAN POPULATION KyuYeongChoi, Tamil Iniyan Gunasekaran, Ji Su Lee, Jang Jae Lee, Na Hyeon Kim, Sa Rang Kang, Wooje Lee, Yu Yong Choi, Hoowon Kim, Kun Ho Lee, National Research Center for Dementia, Chosun University, Gwangju, The Republic of Korea; 2 Department of Premedics, Chosun University, Gwangju, The Republic of Korea; Department of Life Science, Chosun University, Gwangju, The Republic of Korea; School of Medicine, Chosun University/Chosun University Hospital, Gwangju, The Republic of Korea; 5 College of Natural Sciences, Chosun University, Gwangju, The Republic of Korea. Contact e-mail: khaser@gmail.com