Gregory M. Cole, Ph.D.

Department of Neurology & Medicine, David Geffen School of Medicine at UCLA

Associate Director, Geriatric Research Clinical Center GLA VAMC

Director, Gregory Cole Alzheimer Research Laboratory

VA Greater Los Angeles Healthcare System
West Los Angeles Medical Center
11301 Wilshire Blvd., Building 113, Room #312
Los Angeles, CA 90073
Tel: (310) 478-3711 x49727
Email: gregorycole@mednet.ucla.edu

Biography

Dr. Greg M. Cole is currently a Professor of Medicine and Neurology at UCLA, where he is also the Associate Director of the UCLA Alzheimer's Center and Associate Director for Research at the Geriatric Research, Education and Clinical Center for the Greater Los Angeles Veterans Administration System. After receiving undergraduate degrees in Physics and Biochemistry from the University of California at Berkeley and working in an immunology lab at Harvard Medical School, he returned to Berkeley for doctoral work on Alzheimer's and aging (under Professor emeritus Paola Timiras) and then moved to San Diego for postdoctoral work on Alzheimer's at UCSD. His work over the last two decades has been centered on the production and role of beta-amyloid in Alzheimer's disease. Based in part on a series of screens in pre-clinical models, three compounds, R-flurbiprofen, curcumin, and DHA, are already in or under serious consideration for clinical trials. His recent papers investigate the potential for AD prevention with omega 3 fatty acid (DHA, docosahexaenoic acid from fish) and the curry spice extract, curcumin, to control inflammation and oxidative damage and act directly on insoluble amyloid fibrils in plaques and more soluble toxic species in vitro and in vivo. They also explore the role of omega 3, and other dietary fatty acids control the neuroprotective PI3-kinase>Akt pathway, synaptic protein loss, amyloid, and cognitive deficits. Other recent contributions include the co-development of amyloid and tangle PET imaging probes with UCLA colleagues. Much of his work is based on analyzing environmental risk factors, notably NSAIDs, fats and antioxidants, and other anti-amyloid agents for efficacy in animal models for the disease. The primary goal of his lab is to develop safe and widely available methods for the prevention of Alzheimer's and possibly other degenerative diseases of aging.

Specialty

Alzheimer's Disease

Affiliations

COMPLETED - Project 3: Efficacy of New Drugs Directed against Beta Amyloid using in vitro and in vivo Models

Greg Cole Alzheimer Research Laboratory

Research Interests

NSAID inhibition of Alzheimer Pathogenesis: Role of DHA This study investigates impact of DHA depletion by diet and transgene in relation to post-synaptic deficits in relation to PI3-K and PAK signaling pathways.

Program-Project 1: Visualizing Brain A-Beta, Tau and Serotonin Receptor Densities.
This study investigates PET imaging probes for amyloid and tau and neurons using a 3x Tg rat and Tau transgenic mouse model.

Education and Degrees

B.S. Physics/Biochemistry, University of California, Berkeley

Ph.D. Physiology, University of California, Berkeley

Fellow, Alzheimer's Disease, University of California, San Diego

Publications

Arold S, Sullivan P, Bilousova T, Teng E, Miller CA, Poon WW, Vinters HV, Cornwell LB, Saing T, Cole GM, Gylys KH. Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex. Acta Neuropathol 2012;123(1):39-52. PMID: 22020632; PMCID: PMC3404604

Ma QL, Yang F, Frautschy SA, Cole GM. PAK in Alzheimer disease, Huntington disease and X-linked mental retardation. Cell Logist 2012;2(2):117-125. PMID: 23162743; PMCID: PMC3490962

Ma QL, Zuo X, Yang F, Ubeda O, Gant D, Alaverdyan M, Teng E, Hu S, Chen PP, Maiti P, Teter B, Cole GM, Frautschy SA. Curcumin suppresses soluble tau oligomers and corrects molecular chaperone, synaptic and behavioral deficits in aged human tau transgenic mice. J Biol Chem 2012 Dec 21. PMID: 23264626

Ringman JM, Coppola G, Elashoff D, Rodriguez-Agudelo Y, Medina LD, Gylys K, Cummings JL, Cole GM. Cerebrospinal fluid biomarkers and proximity to diagnosis in preclinical familial Alzheimer's disease. Dement Geriatr Cogn Disord 2012;33(1):1-5. doi: 10.1159/000335729. PMID: 22343824

Ringman JM, Elashoff D, Geschwind DH, Welsh BT, Gylys KH, Lee C, Cummings JL, Cole GM. Plasma signaling proteins in persons at genetic risk for Alzheimer disease: influence of APOE genotype. Arch Neurol 2012;69(6):757-764. doi: 10.1001/archneurol.2012.277. PMID: 22689192

Ringman JM, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM. Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther 2012;4(5):43. doi: 10.1186/alzrt146. PMID: 23107780

Ringman JM, Schulman H, Becker C, Jones T, Bai Y, Immermann F, Cole G, Sokolow S, Gylys K, Geschwind DH, Cummings JL, Wan HI. Proteomic changes in cerebrospinal fluid of presymptomatic and affected persons carrying familial Alzheimer disease mutations. Arch Neurol 2012;69(1):96-104. doi: 10.1001/archneurol.2011.642. PMID: 22232349

Roychaudhuri R, Yang M, Deshpande A, Cole GM, Frautschy S, Lomakin A, Benedek GB, Teplow DB. C-Terminal Turn Stability Determines Assembly Differences between Aβ40 and Aβ42. J Mol Biol 2013;425(2):292-308. doi: 10.1016/j.jmb.2012.11.006. PMID: 23154165

Sokolow S, Henkins KM, Bilousova T, Miller CA, Vinters HV, Poon W, Cole GM, Gylys KH. AD synapses contain abundant Aβ monomer and multiple soluble oligomers, including a 56-kDa assembly. Neurobiol Aging 2012;33(8):1545-1555. PMCID: PMC3193864

Sokolow S, Henkins KM, Williams IA, Vinters HV, Schmid I, Cole GM, Gylys KH. Isolation of synaptic terminals from Alzheimer's disease cortex. Cytometry A 2012;81(3):248-254. PMCID: PMC3315390

Frautschy SA, Cole GM. What was lost in translation in the DHA trial is whom you should intend to treat. Alzheimers Res Ther 2011 Jan 20;3(1):2. doi: 10.1186/alzrt61. PMID: 21251328; PMCID: PMC3109411

Cole GM , Frautschy SA. Why pleiotropic interventions are Needed for Alzheimer's disease. Mol Neurobiol. 2010 Jun;41(2-3):392-409.

Cole GM , Frautschy SA. Mechanisms of action of non-steroidal anti-inflammatory drugs for the prevention of Alzheimer's disease. CNS Neurol Disord Drug Targets. 2010 Apr;9(2):140-148.

Cole GM , Frautschy SA. DHA may prevent age-related dementia. J Nutr. 2010;140(4):869-874.

Ercoli LM, Siddarth P, Kepe V, Miller KJ, Huang SC, Cole GM , Lavretsky H, Bookheimer SY, Kim J, Phelps ME, Barrio JR, Small GW. Differential FDDNP PET patterns in nondemented middle-aged and older adults. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 2009;17(5):397-406.

Ma QL, Galasko DR, Ringman JM, Vinters HV, Edland SD, Pomakian J, Ubeda OJ, Rosario ER, Teter B, Frautschy SA, Cole GM. Reduction of SorLa/LR11, a sorting protein limiting beta-amyloid production, in Alzheimer Disease Cerebrospinal Fluid.  Arch Neurol 2009 Apr;66(4):448-457.

Hu S, Begum AN, Jones MR, Oh MS, Beech WK, Beech BH, Yang F, Chen P, Ubeda OJ, Kim PC, Davies P, Ma Q, Cole GM , Frautschy SA. GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adverse effects in control animals. Neurobiol Dis 2009 Feb;33(2):193-206. Epub 2008 Nov 5.

Begum AN, Yang F, Teng E, Hu S, Jones MR, Rosario ER, Beech W, Hudspeth B, Ubeda OJ, Cole GM, Frautschy SA. Use of copper and insulin-resistance to accelerate cognitive deficits and synaptic protein loss in a rat Abeta-infusion Alzheimer's disease model. J Alzheimers Dis 2008 Dec;15(4):625-640.

Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull K, Teter B, Cole GM , Frautschy SA. Curcumin structure-function, bioavailablity and efficacy in models of neuroinflammation and Alzheimer’s.  J Pharmacol Exp Ther 2008 Jul;326(1):196-208.

Ma QL, Yang F, Calon F, Ubeda OJ, Hansen JE, Weisbart RH, Beech W, Frautschy SA, Cole GM .  P21-activated kinase aberrant activation and translocation in Alzheimer's disease pathogenesis. rrant activation and translocation in Alzheimer disease pathogenesis. J Biol Chem 2008 May 16;283(20):14132-14143.

Fein JA, Sokolow S, Miller CA, Vinters HV, Yang F, Cole GM , Gylys KH. Colocalization of amyloid beta and tau pathology in AD synaptosomes. Am J Pathol 2008 Jun;172(6):1683-1692. Epub 2008 May 8.

Small GW, Siddarth P, Burggren AC, Kepe V, Ercoli LM, Miller KJ, Lavretsky H, Thompson PM, Cole GM , Huang SC, Phelps ME, Bookheimer SY, Barrio JR. Influence of cognitive statusm, age and ApoE4 genetic reisk on brain FDDNP PET binding in non demented persons. Arch Gen Psychiatry 2009;66(1):81-87.

Small GW, Bookheimer SY, Thompson PM, Cole GM , Huang SC, Kepe V, Barrio JR. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurology 2008 Feb;7(2):161-172.

Ma QL, Teter B, Ubeda OJ, Morihara T, Dhoot D, Nyby MD, Tuck ML, Frautschy SA, Cole GM.  Omega-3 Fatty Acid Docosahexaenoic Acid Increases Sorla/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer Disease (AD): Relevance to AD Prevention.  Journal of Neuroscience December 26, 2007;27(52):14299 –14307.

Ringman JM , Younkin SG, Pratico D, Seltzer W, Cole GM , Geschwind DH, Rodriguez Y, Schaffer B, Fein J, Gylys KH, Varpetian A, Medina LD, Cummings JL. Biochemical Markers in Persons with Pre-Clinical Familial Alzheimer's Disease. Neurology 2008 Jul 8;71(2):85-92. Epub 2008 May 28.