Research Topics
| G M ColeSummaryAffiliation: University of California Country: USA Publications
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Publications
What was lost in translation in the DHA trial is whom you should intend to treatSally A Frautschy
Veterans Greater Los Angeles Healthcare System, Geriatric Research Education and Clinical Center, 16111 Plummer St, North Hills, CA 91343, USA
Alzheimers Res Ther 3:2. 2011..should preclinical and clinical studies be performed to optimize dose and mitigate oxidation before pursuing intervention or prevention trials with DHA? And finally, should DHA be tested now for mild cognitive impairment or prevention?..
NSAID and antioxidant prevention of Alzheimer's disease: lessons from in vitro and animal modelsGreg M Cole
Greater Los Angeles Healthcare System, Veterans Administration Medical Center, North Hills, CA 91343, USA
Ann N Y Acad Sci 1035:68-84. 2004..Curcumin directly targeted Abeta and was also effective in other models, warranting further preclinical and clinical exploration...- Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer's disease mouse modelGreg M Cole
Greater Los Angeles Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center, California, USA
Nutr Health 18:249-59. 2006..Many Western diets are typically deficient in DHA and low in polyphenolic antioxidant intake. These and other data argue that increasing dietary intake of both DHA and polyphenolic antioxidants may be useful for AD prevention... - Neuroprotective effects of curcuminGreg M Cole
Greater Los Angeles Veterans Affairs Healthcare System, Geriatric Research, Education, and Clinic Center, Sepulveda, CA 91343, USA
Adv Exp Med Biol 595:197-212. 2007..Promising results have already led to ongoing pilot clinical trials... - Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventionsGreg M Cole
Greater Los Angeles Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center, Sepulveda, CA 91343, USA
Neurobiol Aging 26:133-6. 2005..Both DHA and curcumin have favorable safety profiles, epidemiology and efficacy, and may exert general anti-aging benefits (anti-cancer and cardioprotective.)... 
Omega-3 fatty acids and dementiaGreg M Cole
Department of Medicine at University of California, Los Angeles, CA, USA
Prostaglandins Leukot Essent Fatty Acids 81:213-21. 2009..Clinical trials are underway to prevent and treat AD. Results to-date suggest that DHA may be more effective if it is begun early or used in conjunction with antioxidants...- The role of insulin and neurotrophic factor signaling in brain aging and Alzheimer's DiseaseGreg M Cole
Greater Los Angeles Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center, 16111 Plummer Street, Sepulveda, CA 91343, USA
Exp Gerontol 42:10-21. 2007..A better understanding of the precise mechanisms underlying alterations in the insulin/neurotrophic factor signal transduction pathways should aid the search for better AD therapeutic and prevention strategies... - Alzheimer's amyloid story finds its starGreg M Cole
Department of Medicine and Neurology, UCLA SFVP and GLAVA GRECC 11E, 16111 Plummer, North Hills, CA 91343, USA
Trends Mol Med 12:395-6. 2006..These authors used a transgenic mouse model to identify a specific type of aggregate that emerges with cognitive deficits and is capable of transmitting a spatial memory defect to unimpaired animals... - Influence of lipoproteins on microglial degradation of Alzheimer's amyloid beta-proteinG M Cole
Sepulveda VA Medical Center, Sepulveda, California 91343, USA
Microsc Res Tech 50:316-24. 2000.... - Dietary fatty acids and the aging brainGreg M Cole
Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA
Nutr Rev 68:S102-11. 2010..Evidence presented here shows DHA acts to oppose this, exerting a plethora of pleiotropic activities to protect against the pathogenesis of Alzheimer's disease... - DHA may prevent age-related dementiaGreg M Cole
Departments of Medicine and Neurology, University of California, Los Angeles, CA 90095, USA
J Nutr 140:869-74. 2010..We advocate early intervention in a prodromal period with nutrigenomically defined subjects with an appropriately designed nutritional supplement, including DHA and antioxidants... - Lipoprotein effects on Abeta accumulation and degradation by microglia in vitroG M Cole
Sepulveda VAMC, GRECC, and Departments of Medicine and Neurology, University of California Los Angeles, Sepulveda 91343, USA
J Neurosci Res 57:504-20. 1999..These data suggest that lipoprotein-dependent Abeta trafficking to microglia could be relevant to plaque pathogenesis in AD... - Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathologyS A Frautschy
VAGLAHS Sepulveda GRECC, Departments of Medicine and Neurology, UCLA, 16111 Plummer Street, North Hills, CA, USA
Neurobiol Aging 22:993-1005. 2001..Because of its low side-effect profile and long history of safe use, curcumin may find clinical application for AD prevention... - Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic miceG P Lim
VAGLAHS-Sepulveda GRECC, Departments of Medicine and Neurology, UCLA, Los Angeles, CA, USA
Neurobiol Aging 22:983-91. 2001..05). Although interleukin-1beta and insoluble Abeta were more effectively reduced with longer treatment, the magnitude of the effect on soluble Abeta was not dependent on treatment duration... - Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer's diseaseE D Agdeppa
Division of Nuclear Medicine, Department of Molecular and Medical Pharmacology, Laboratory of Structural Biology and Molecular Medicine, University of California Los Angeles School of Medicine, Los Angeles, California 90095, USA
J Neurosci 21:RC189. 2001.... - Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's diseaseG P Lim
University of California Los Angeles, Departments of Medicine and Neurology, 90095, USA
J Neurosci 20:5709-14. 2000.... - The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouseG P Lim
Departments of Medicine and Neurology, University of California, Los Angeles, Los Angeles, California 90095, USA
J Neurosci 21:8370-7. 2001..Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease... - Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcuminQiu Lan Ma
Department of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA
J Neurosci 29:9078-89. 2009.... - A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse modelGiselle P Lim
Department of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA
J Neurosci 25:3032-40. 2005..Together, these results suggest that dietary DHA could be protective against beta-amyloid production, accumulation, and potential downstream toxicity... - Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's diseaseF Yang
Department of Medicine and Neurology, UCLA, Los Angeles, California, USA
Am J Pathol 152:379-89. 1998..In situ detection of caspase-cleaved actin provides a new means to evaluate the role of caspase activation in pathological and physiological processes... - Defective neuronal sprouting by human apolipoprotein E4 is a gain-of-negative functionB Teter
Veterans Administration Greater Los Angeles Healthcare System and Department of Medicine, University of California, Los Angeles, Sepulveda, California 91343, USA
J Neurosci Res 68:331-6. 2002..These results may have important pharmacogenomic implications for AD therapies that modulate apoE expression levels... - Selective inhibition of Abeta42 production by NSAID R-enantiomersT Morihara
Department of Medicine, University of California, Los Angeles, California, USA
J Neurochem 83:1009-12. 2002..Because of its efficacy at lowering Abeta42 production and low toxicity profile, R-flurbiprofen is a strong candidate for clinical development... - Estrogen (E2) and glucocorticoid (Gc) effects on microglia and A beta clearance in vitro and in vivoM E Harris-White
Department of Medicine, UCLA, C-128 RNRC, Los Angeles, CA 90095-1769, USA
Neurochem Int 39:435-48. 2001..The failure of both steroids to accelerate A beta degradation may explain their lack of efficacy for treatment of AD... - Cat and mouseGreg M Cole
Greater Los Angeles Healthcare System, Veterans Administration Medical Center, Geriatric Research Education Clinical Center, North Hills, California 91343, USA
Neuron 51:671-2. 2006..manipulate the expression of cathepsin B in aged APP transgenic mice, observing that increased expression degrades preformed oligomeric and fibrillar amyloid, while inactivation accelerates beta-amyloidosis... - Antibodies against beta-amyloid reduce Abeta oligomers, glycogen synthase kinase-3beta activation and tau phosphorylation in vivo and in vitroQiu-Lan Ma
Department of Medicine, University of California, Los Angeles, California 91343, USA
J Neurosci Res 83:374-84. 2006..These data suggest that antibodies that are highly specific for toxic oligomer subspecies may reduce toxicity via reduction of GSK-3beta, which could be an important strategy for Alzheimer's disease (AD) therapeutics... - Reduction of SorLA/LR11, a sorting protein limiting beta-amyloid production, in Alzheimer disease cerebrospinal fluidQiu Lan Ma
Department of Medicine, University of California, Los Angeles, California, USA
Arch Neurol 66:448-57. 2009..LR11 protein is reduced in patients with late-onset AD, and LR11 polymorphisms have been associated with late-onset AD... - In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer's brain using the positron emission tomography molecular imaging probe 2-(1-[6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrileE D Agdeppa
Division of Nuclear Medicine, Department of Molecular and Medical Pharmacology, Laboratory of Structural Biology and Molecular Medicine, The David Geffen School of Medicine at UCLA, Box 956948, Los Angeles, CA 90095, USA
Neuroscience 117:723-30. 2003.... - Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's diseaseFrederic Calon
Department of Medicine, University of California, Los Angeles, California, USA
Eur J Neurosci 22:617-26. 2005..The marked effect of dietary n-3 PFA on NMDA receptors and caspase/calpain activation in the cortex of an animal model of AD provide new insights into how dietary essential fatty acids may influence cognition and AD risk... - Biochemical markers in persons with preclinical familial Alzheimer diseaseJ M Ringman
UCLA Department of Neurology, Alzheimer Disease Research Center, 10911 Weyburn Ave, Suite 200, Los Angeles, CA 90095 7226, USA
Neurology 71:85-92. 2008..Persons at risk for familial Alzheimer disease (FAD) provide a model in which biomarkers can be studied in presymptomatic disease... - Quantitative characterization of crude synaptosomal fraction (P-2) components by flow cytometryK H Gylys
UCLA School of Nursing, Los Angeles, California 90095 6919, USA
J Neurosci Res 61:186-92. 2000..These results suggest that flow cytometry may be used to take advantage of the increased viability, yield, and convenience of the P-2 fraction for studies of nerve terminal function... - Current and future uses of neuroimaging for cognitively impaired patientsGary W Small
Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California, USA
Lancet Neurol 7:161-72. 2008.... - Use of copper and insulin-resistance to accelerate cognitive deficits and synaptic protein loss in a rat Abeta-infusion Alzheimer's disease modelAynun N Begum
Department of Medicine, University of California, Los Angeles, CA, USA
J Alzheimers Dis 15:625-40. 2008..In summary, the newly described in vivo infusion model may be useful cost-effective method for screening for new therapeutic drugs for AD... - GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adverse effects in control animalsShuxin Hu
Greater Los Angeles Healthcare System, Geriatric Research Education and Clinical Center, Veteran s Affairs Medical Center, USA
Neurobiol Dis 33:193-206. 2009..These data support a role for GSK3 hyperactivation in AD pathogenesis, but emphasize the importance of developing inhibitors that do not suppress constitutive activity... - Cell type specific targeted intracellular delivery into muscle of a monoclonal antibody that binds myosin IIbRichard H Weisbart
Department of Medicine, Division of Rheumatology, Veterans Affairs Greater Los Angeles Health Care System, Sepulveda, CA 91343, USA
Mol Immunol 39:783-9. 2003..Myosin IIb is implicated in the specific targeting of mAb 3E10 to skeletal muscle... - PET of brain amyloid and tau in mild cognitive impairmentGary W Small
Department of Psychiatry and Biobehavioral Sciences and the Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, USA
N Engl J Med 355:2652-63. 2006..Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics... - Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD preventionQiu Lan Ma
Department of Medicine, University of California, Los Angeles, California 90095, USA
J Neurosci 27:14299-307. 2007..Because reduced LR11 is known to increase Abeta production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD... - Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer diseaseLixia Zhao
Greater Los Angeles Veterans Affairs Healthcare System, Sepulveda, California 91343, USA
Nat Neurosci 9:234-42. 2006.... - Influence of cognitive status, age, and APOE-4 genetic risk on brain FDDNP positron-emission tomography imaging in persons without dementiaGary W Small
Semel Institute, 760 Westwood Plaza, Ste 88 201, Los Angeles, CA 90024, USA
Arch Gen Psychiatry 66:81-7. 2009..Here we investigated whether known risk factors for Alzheimer disease and dementia are associated with FDDNP-PET binding... - Why pleiotropic interventions are needed for Alzheimer's diseaseSally A Frautschy
Geriatric Research and Clinical Center, Greater Los Angeles Healthcare System, Veteran s Administration, Los Angeles, USA
Mol Neurobiol 41:392-409. 2010.... - Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse modelFrederic Calon
Department of Medicine, University of California, Los Angeles, 90095, USA
Neuron 43:633-45. 2004..Since n-3 PFAs are essential for p85-mediated CNS insulin signaling and selective protection of postsynaptic proteins, these findings have implications for neurodegenerative diseases where synaptic loss is critical, especially AD... - Antibody-mediated transduction of p53 selectively kills cancer cellsRichard H Weisbart
Division of Rheumatology, Department of Medicine, Veterans Affairs Greater Los Angeles Health Care System, Sepulveda, CA 91343, USA
Int J Oncol 25:1867-73. 2004..Fv-p53 was shown to penetrate cancer cells engrafted in vivo. These results support continued efforts to evaluate the potential efficacy of Fv-p53 for the treatment of certain cancers in vivo... - Apoptosis in a neonatal rat model of cerebral hypoxia-ischemiaM R Pulera
Department of Neurology, Veteran s Affairs Medical Center, Sepulveda, Calif, USA
Stroke 29:2622-30. 1998..BACKGROUND and.. - Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease interventionLixia Zhao
Department of Medicine, University of California Los Angeles, California 91343, USA
J Neurosci 24:11120-6. 2004..These in vitro and in vivo analyses validate the use of enhanced CNS insulin signaling as a potential strategy for AD intervention to correct the IDE defects occurring in AD... - Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's diseaseAynun N Begum
Department of Medicine, University of California, Los Angeles, California, USA
J Pharmacol Exp Ther 326:196-208. 2008.... - Ibuprofen suppresses interleukin-1beta induction of pro-amyloidogenic alpha1-antichymotrypsin to ameliorate beta-amyloid (Abeta) pathology in Alzheimer's modelsTakashi Morihara
Greater Los Angeles VA Healthcare System, GRECC, Sepulveda, CA, USA
Neuropsychopharmacology 30:1111-20. 2005..We present evidence supporting the hypothesis that ibuprofen-dependent amyloid reduction is mediated by inhibition of an alternate pathway (IL-1beta and its downstream target ACT)... - Mechanisms of action of non-steroidal anti-inflammatory drugs for the prevention of Alzheimer's diseaseGreg M Cole
Geriatric Research and Education Center, North Hills, CA 91343, USA
CNS Neurol Disord Drug Targets 9:140-8. 2010..This encourages researchers to re-address possible mechanisms for a stage-dependent NSAID efficacy, the subject of this review... - Evidence of Abeta- and transgene-dependent defects in ERK-CREB signaling in Alzheimer's modelsQiu Lan Ma
Department of Medicine, University of California, Los Angeles, California, USA
J Neurochem 103:1594-607. 2007..These effects were reversed by anti-oligomer. Our data strongly support the existence of an APPsw transgene-dependent and Abeta oligomer-mediated defect in regulation of ERK activation... - p21-activated kinase-aberrant activation and translocation in Alzheimer disease pathogenesisQiu Lan Ma
Department of Medicine, UCLA, Los Angeles, California, USA
J Biol Chem 283:14132-43. 2008..Our results implicate aberrant PAK in Abeta oligomer-induced signaling and synaptic deficits in Alzheimer disease... - Ironic fate: can a banned drug control metal heavies in neurodegenerative diseases?Greg M Cole
Greater Los Angeles VA Medical Center, UCLA Alzheimer s Disease Research Center, Sepulveda, CA 91343, USA
Neuron 37:889-90. 2003..This raises the issue of specific iron chelators or clioquinol for control of oxidative damage in Parkinson's, Alzheimer's, and other neurodegenerative diseases, but not without safety concerns... - Role of apolipoprotein E and estrogen in mossy fiber sprouting in hippocampal slice culturesB Teter
Greater Los Angeles Veteran s Healthcare System, Sepulveda, and Department of Medicine, University of California, Los Angeles, 91343, USA
Neuroscience 91:1009-16. 1999..Estrogen and apolipoprotein E may therefore interact in their modulation of both Alzheimer's disease risk and recovery from CNS injury... - Caspase inhibition protects nerve terminals from in vitro degradationKaren H Gylys
UCLA School of Nursing, Brain Research Institute, Box 956919, Los Angeles, California 90095, USA
Neurochem Res 27:465-72. 2002..These results indicate activation of both caspase and calpain in the P-2 fraction and suggest a role for these cysteine proteases in the in vitro degradation of nerve terminals... - Enrichment of presynaptic and postsynaptic markers by size-based gating analysis of synaptosome preparations from rat and human cortexKaren H Gylys
UCLA School of Nursing and Brain Research Institute, UCLA School of Medicine, Los Angeles, California 90095, USA
Cytometry A 60:90-6. 2004.... - Increased cholesterol in Abeta-positive nerve terminals from Alzheimer's disease cortexKaren Hoppens Gylys
UCLA School of Nursing, Los Angeles, CA 90095, USA
Neurobiol Aging 28:8-17. 2007..These results suggest that Abeta accumulation in synaptic terminals may underly dysfunction prior to or independent of extracellular amyloid deposition... - Rapid annexin-V labeling in synaptosomesKaren H Gylys
UCLA School of Nursing and Brain Research Institute, Box 956919, Factor Building, Los Angeles, CA 90095, USA
Neurochem Int 44:125-31. 2004..These data demonstrate that PS externalization and caspase activation occur rapidly in this widely used neurochemical preparation... - Intracellular Abeta is increased by okadaic acid exposure in transfected neuronal and non-neuronal cell linesXiaoyan Sun
Laboratory for Alzheimer's Disease, Brain Science Institute of the RIKEN, 2-1 Hirosawa, Wako, 351-0198, Saitama, Japan
Neurobiol Aging 23:195-203. 2002..The increased full-length APP and decreased APPC99 were also observed. This is the first study to demonstrate that OA treatment significantly increases intracellular Abeta... - A potential role of the curry spice curcumin in Alzheimer's diseaseJohn M Ringman
University of California, Los Angeles, Department of Neurology, Alzheimer s Disease Research Center, Los Angeles, CA 90095, USA
Curr Alzheimer Res 2:131-6. 2005..We are therefore performing a study of curcumin in patients with AD to gather this information in addition to data on the effect of curcumin on biomarkers of AD pathology... - Synaptic changes in Alzheimer's disease: increased amyloid-beta and gliosis in surviving terminals is accompanied by decreased PSD-95 fluorescenceKaren Hoppens Gylys
UCLA School of Nursing and Brain Research Institute, Box 956919 Factor Bldg, Los Angeles, CA 90095 6919, USA
Am J Pathol 165:1809-17. 2004.... - Apolipoprotein E enhances uptake of soluble but not aggregated amyloid-beta protein into synaptic terminalsKaren H Gylys
UCLA School of Nursing and Brain Research Institute, UCLA School of Medicine, Los Angeles, California 90095 6919, USA
J Neurochem 84:1442-51. 2003..These results suggest that complex formation with apoE enhances internalization of soluble Abeta uptake into terminals... - Co-localization of amyloid beta and tau pathology in Alzheimer's disease synaptosomesJeffrey A Fein
School of Nursing, University of California at Los Angeles School of Medicine, Sepulveda Veterans Administration Medical Center, Los Angeles, California 90095 6919, USA
Am J Pathol 172:1683-92. 2008..0001). These results showing overlapping Abeta and tau pathology are consistent with a model in which both synaptic loss and dysfunction are linked to a synaptic amyloid cascade within the synaptic compartment... - Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivoFusheng Yang
Department of Medicine, UCLA, Los Angeles, CA 90095, USA
J Biol Chem 280:5892-901. 2005..These data suggest that low dose curcumin effectively disaggregates Abeta as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD... - Serotonin 1A receptors in the living brain of Alzheimer's disease patientsVladimir Kepe
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Proc Natl Acad Sci U S A 103:702-7. 2006.... - The microglial phagocytic role with specific plaque types in the Alzheimer disease brainMichael R D'Andrea
Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, D404, Spring House, PA 19477, USA
Neurobiol Aging 25:675-83. 2004..In summary, the data presented suggests that plaque associated microglial activation is typically subsequent to specific amyloid plaque formations in the AD brain...
Research Grants
- NSAID Inhibition of Alzheimer Pathology: Role of DHAGregory M Cole; Fiscal Year: 2010..Understanding dietary fatty acid /Abeta-related PAK complex deficits and downstream synaptic defects will reveal a poorly studied overlap between cognitive deficits in mental retardation syndromes and AD with therapeutic implications. ..