Select a year 1998 1999 2000 2001 2002 2003    Select a researcher Shawn Cameron Ahmed, B.S., Ph.D. Yidong Bai, Ph.D. Antonio Bedalov, M.D., Ph.D. Michael J. Bertram, Ph.D. Dominique Broccoli, Ph.D. Cindy X. Cai, M.D., Ph.D. Phillip Carpenter, Ph.D. Sandy Chang, M.D.,Ph.D Phillip A. Cole, M.D., Ph.D Ana Maria Cuervo, M.D., Ph.D. Jay M. Edelberg, Ph. D. Michael D. Ehlers, M.D., Ph.D. Stewart Frankel, Ph.D. Jeffrey S. Friedman, Ph. D. Wen-Biao Gan, Ph. D. Roman Giger, Ph.D. Todd Golde, M.D., Ph.D Vera Gorbunova, Ph.D. Shiv L. S. Grewal, Ph.D. Francine Grodstein, Sc.D. Ya Ha, Ph.D. Bruce Hay, Ph.D. Yasunori Hayashi, M.D., Ph.D. Mike Hutton, Ph. D. Shin-ichiro Imai, M.D., Ph.D. Michael Gordon Kaplitt, M.D., Ph.D. Tae-Wan Kim, Ph.D. Shuji Kishi, M.D., Ph.D. Steven Lyle, M.D., Ph.D. Jiyan Ma, Ph.D. Kyung-Tai Min, Ph.D. Danesh Moazed, Ph.D. William A. Mohler, Ph.D. Kathryn J. Moore, Ph.D. Elly Nedivi, Ph.D. David K. Orren, Ph. D. Giovanni Paternostro, M.D., Ph.D. Henry L. Paulson, M.D., Ph.D. Jacob Raber, Ph.D. Tannishtha Reya, Ph.D. Brad A. Rikke, Ph.D. Jeff J. Sekelsky, Ph. D. Robert Sheaff, Ph.D. Hong-Bing Shu, Ph. D. David A. Sinclair, Ph.D. James E. Sligh, M.D., Ph. D. Zhou Songyang, Ph.D. Peiqing Sun, Ph. D. Marc Tatar, Ph. D. Anthony D. Wagner, Ph. D. David Q.H. Wang, M.D., Ph.D. Weidong Wang, Ph.D. David G. Wells, Ph.D. Stephen Robert Wicks, Ph.D. Huaxi Xu, Ph.D. Hong Yan, Ph.D. Hui Zheng, Ph. D. Select a project A Genetic Approach to Identification of Genes Involved in ...A Mechanistic Explanation for the Development of Neurodege...Age-related Changes in the Functional Neurobiology of MemoryAging and Cholesterol Gallstone Formation: Molecular Mecha...Altered Mitochondrial Function in Transgenic Models of Cut...An Inducible Gene Knockout System for Alzheimer's Dise...ApoptosisBiochemical Characterization of a Putative p53-binding Pro...Characterization of a Novel Protein Complex Involved in th...Chemical Genetic Approaches to AgingConnections Between the Nucleolus and Cellular AgingControl of stem cell self-renewal and regenerationCPG15, A Novel Growth Promoting Molecule Involved in Synap...Effect of Aging on Efficiency and Accuracy of DNA Double-S...Effect of PTEN Anti-Oncogene on Age-Related Neurodegenerat...Estrogen, Antioxidants, and Cognitive Function in WomenFunctional Analysis of Aging and Cell Survival Signal Path...Functional Characterization of a Drosophila RecQ HelicaseGender and Isoform-Specific Effects of ApoE on Cognition i...Genetic Analysis of Cardiac Aging in DrosophilaGenetic Analysis of the MORF4 Related Gene Family in Droso...Genetic and Functional Analysis of CD36-signaling in Age-r...Genetic and functional analysis of mitochondrial DNA mutat...Genetic Approaches for Functional Aging in ZebrafishGenetic Studies of Factors Controlling Amyloid ProductionGenomic Instability and Aging in Werner-Telomerase Compoun...Germline Immortality in C. elegansGonadal Steroid Regulation of ß-Amyloid Generation: ...Heterochromatin Assembly and Replicative Life-Span in Fiss...Identification of Genes and Compounds that Extend Yeast Li...Identification of Proteins Functionally Redundant to the W...In Vivo Analysis of the Role of Tau in Neurodegeneration.In Vivo Study of Age-related Changes in Synaptic StructureInhibition of N-acetyltransferaseLife Extension of Drospohila by a Drug TreatmentMechanisms of Neural Plasticity in the Mammalian SystemMechanisms of Neuronal Dysfunction and Death in Neurodegen...Molecular and Cell Biology of Adult Epithelial Stem CellsMolecular Mechanisms of Age-Related Changes at Hippocampal...Molecular Mechanisms of Telomere Dependent SenescenceNatural Sequence Variation in C. elegans: Impact on...Neuroendocrine Regulation of Aging in DrosophilaNew Approaches to Characterizing Cellular Changes in Sarco...Nuclear Ferritin May Protect Against Oxidative and Light-i...Presenilins and Gamma-Secretase Cleavage of the Amyloid Be...QTLs Specifying the Retardation of Reproductive Senescence...Regulation of Senescent Angiogenic PotentialRestoration of chaperone-mediated autophagy activity in ol...Role of Neural Progenitors in Adult Hippocampal- and Olfac...Signaling by Tumor Necrosis Factor Family MembersStructural studies of human y-secretaseSynaptic Plasticity in the Aging Brain: Role of CPE-depend...The Function of Mammalian NAD-dependent deacetylase Sir2The Pathogenic Mechanism of Prion DiseaseThe Regulation of Chromosomes and LongevityThe Role of p66shc in Cellular Senescence and M...Understanding the Role of Genomic Instability in Human Agi... Select an institution Albert Einstein College of Medicine of Yeshiva University Baylor College of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School Boston College Brigham and Women's Hospital, Harvard Medical School Brown University Burnham Institute California Institute of Technology Cold Spring Harbor Laboratory Columbia University Cornell University Dana Farber Cancer Institute, Harvard Medical School Duke University Medical Center Fox Chase Cancer Center Fred Hutchinson Cancer Research Center Harvard Medical School M.D. Anderson Cancer Center Massachusetts General Hospital Massachusetts Institute of Technology Mayo Clinic, Jacksonville National Institute of Neurological Disorders and Stroke, National Institutes of Health National Institute on Aging, National Institutes of Health National Jewish Medical Center Ohio State University Oregon Health & Science University Rockefeller University Scripps Research Institute Skirball Institute - New York University School of Medicine Stanford University Tufts University School of Medicine University of Alabama - Birmingham University of Colorado - Boulder University of Connecticut Health Center University of Iowa University of Kentucky Chandler Medical Center University of Minnesota Cancer Center University of North Carolina - Chapel Hill University of Rochester Medical Center University of Texas Health Science Center - San Antonio University of Texas Medical School - Houston Vanderbilt University School of Medicine Washington University School of Medicine Weill Medical College of Cornell University Yale University School of Medicine

Jacob Raber, Ph.D. Oregon Health & Science University

The three major human apolipoprotein (apo) E isoforms are encoded by distinct alleles (e 2, e 3, and e 4). Compared with e 2 and e 3, e 4 increases the risk of cognitive impairments and of developing Alzheimer’s disease (AD). ApoE4 interacts with female gender, resulting in an even greater risk of developing AD and in a diminished treatment response. ApoE4 might also be associated with an accelerated AD decline, but this remains controversial. Consistent with these human data, our data show that in transgenic mice expressing human apoE isoforms in the brain and lacking mouse apoE (Apoe-/-) female, but not male, apoE4 mice develop progressive impairments in spatial and nonspatial learning and memory, compared with age- and sex-matched wild-type, Apoe-/- or apoE3 mice. This could be relevant to cognitive impairments in human e 4 carriers. Because the cognitive impairments are observed in female apoE4 mice that express apoE4 in neurons or astrocytes, they are independent of the cellular source of apoE. Sex steroids might contribute to the gender-dependent effects of apoE4. Treatment with testosterone or dihydrotestosterone, a testosterone derivative that cannot be aromatized to 17-b estradiol, antagonizes the cognitive deficits of adult apoE4 female mice. In addition, adult apoE4 male mice, which do not show cognitive deficits in the water maze, develop them after blockade of androgen receptors, whereas apoE3 male mice do not.

We will develop virtual reality (VR) testing to bridge the gap between spatial learning and memory in healthy elderly and elderly with cognitive disorders and animal models of these illnesses. VR testing enables the use of paradigms similar to those used in animal studies and provides objective performance measures. In humans, spatial memory tests to assess visual-spatial memory are routinely used in which all the information is within one field of view and the subject has an aerial perspective and a body-centered (egocentric) frame of reference (table-top tests). Such tests are very different from spatial memory tests comparable to those used in rodents in which all the information is throughout a complex environment in which the subject navigates and has a viewer perspective and a word-centered (allocentric) frame of reference. In our VR setup, the subject sits in a motorized vehicle and is immersed in a computer-generated virtual world, through a head-mounted display (HMD) system comprised of special LCD video goggles and headphones, that changes with head and body motion. Inside the visor of the helmet are one video screen for each eye, generating a 3-dimensional experience, and two earphones presenting stereo sounds coinciding with the visual images. A transmitter on the HMD allows the computer to monitor changes in head position and to generate a corresponding point-of-view. Each back tire of the motorized vehicle is placed on its own set of rollers, allowing both wheels to move independently. Encoders built into the roller assembly enable the computer to determine the speed and direction of the motion. Using VR testing, we will assess interactions between apoE genotype and cognition in elderly males and females who are healthy, have mild cognitive impairment (MCI), or have AD. These studies will help to elucidate the roles of apoE isoforms in the brain. This is important for our understanding of cognitive function in health as well as in diseases characterized by cognitive impairments and will likely advance the development of therapeutic intervention to prevent or even reverse cognitive impairments.

Contact Dr. Raber.