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 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 an analysis of 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.
- Selected peer-reviewed publications (in chronological order).
Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yanf F, Cole G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996 Oct 4;274(5284):99-102.
Frautschy SA, Yang F, Irrizarry M, Hyman B, Saido TC, Hsiao K, Cole GM. The microglial response to amyloid plaques in APPsw transgenic mice. Am. J. Pathol. 1998;152:307-317.
Cummings JL, Vinters HV, Cole, GM, Khachaturian ZS. Alzheimer’s Disease: Etiologies, Pathophysiology, Cognitive Reserve, and Treatment Opportunities. Neurology 1998;51:s2-s17.
Frautschy SA, Horn DL, Yang F, Mendoza JJ, Sigel JJ, Harris-White ME, Cole GM. Protease inhibitor co-infusion with Aß results in enhanced deposition and toxicity in rat brain. J. Neurosci. 1998;18:8311-8321.
Pulera MR, Adams LM, Liu H, Santos DG, Nishimura RN, Yang F, Cole GM, Wasterlain CG. Apoptosis in a neonatal rat model of cerebral hypoxia- ischemia. Stroke 1998;29:2622-2630.
Cole GM, Beech W, Frautschy SA, Sigel J, Glasgow C, Ard MD. Lipoprotein effects on Aß accumulation and degradation by microglia in vitro. J. Neurosci. Res. 1999;57:504-520.
Teter B, Beech W, Harris-White M, Frautschy SA, Cole GM. Role of Apolipoprotein E and estrogen in mossy fiber sprouting in hippocampal slice cultures. Neuroscience 1999;91:1009-1016.
Teter B, Xu P-T, Gilbert J R, Roses AD, Galasko D, Cole GM. Human Apo E isoform-specific differences in neuronal sprouting in organotypic hippocampal slice culture. J. Neurochem. 1999;73(6):2613-2616.
Mega MS, Chu T, Mazziotta JC, Trivedi KH, Thompson PM, Shah A, Cole G, Frautschy SA, Toga AW. Mapping biochemistry to metabolism: FDG-PET and amyloid burden in AD. Neuroreport 1999;10:2911-7.
Yang F, Ueda K, Chen PP, Ashe KH, Cole GM. Plaque-associated a-synuclein (NACP) pathology in aged transgenic mice expressing amyloid precursor protein. Brain Res. 2000;853:381-383.
Rossiter JP, Anderson LL, Srinivasan A, Yang F, Cole GM. Caspase-cleaved actin (fractin) immunolabelling of Hirano bodies. Neuropathology and Appl. Neurobiology 2000;26(4):342-346.
Cole GM and Ard M. Influence of lipoproteins on microglial degradation of Alzheimer’s Aß. Micro. Res. Tech. 2000;50:316-324.
Lankewicz S, Luetjens CM, Bui NT, Krohn AJ, PoppeM, Cole GM, Nicholson DW, Saido TC, Prehn JHM. Activation of calpain I converts excitotoxic neuron death into a caspase-independent cell death. J. Biol. Chem. 2000;275:17064-17071.
Lim GP, Yang F, Chu T, Chen P, Beech W, Teter B, Tran T, Ubeda O, Hsiao K Ashe, Frautschy SA, Cole GM. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s Disease. J. Neurosci. 2000;20:5709-5714.
Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Neuroscience 2001;21:8370-8377.
Lim GP, Yang F, Chu T, Gahtan E, Ubeda O, Beech W, Overmier JB, Hsiao Ashe K, Frautschy SA, Cole GM. Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice. Neurobiology of Aging. 2001;22:983-991.
Tomioka M, Shirotani K, Iwata N, Lee HJ, Yang F, Cole GM, Seyama Y, Saido TC. In vivo role of caspases in excitotoxic neuronal death: generation and analysis of transgenic mice expressing baculoviral caspase inhibitor, p35, in postnatal neurons. Brain Res Mol Brain Res. 2002 Dec;108(1-2):18-32.
Morihara T, Chu T, Ubeda O, Beech W, Cole GM. Selective inhibition of Abeta42 production by NSAID R-enantiomers. J Neurochem. 2002 Nov;83(4):1009-12.
Gylys KH, Fein JA, Cole GM. Caspase inhibition protects nerve terminals from in vitro degradation. Neurochem Res. 2002 Jun;27(6):465-72.
Teter B, Xu PT, Gilbert JR, Roses AD, Galasko D, Cole GM. Defective neuronal sprouting by human apolipoprotein E4 is a gain-of-negative function. J Neurosci Res. 2002 May 1;68(3):331-6.
Cummings, JL, Cole, GM. Alzheimer Disease. JAMA 2002;287:2335-2338.
Cole GM, Yang F, Lim GP, Cummings JL, Masterman DL, Frautschy SA. A rationale for curucminoids for the prevention or treatment of AD. Curr. Med. Chem-Immun.,Endoc. & Metab. Agents 2003;3: 15-25.
Cole GM. Ironic fate: can a banned drug control metal heavies in neurodegenerative diseases? Neuron. 2003 Mar 27;37(6):889-90.
Weisbart RH, Yang F, Chan G, Wakelin R, Ferreri K, Zack DJ, Harrison B, Leinwand LA, Cole GM. Cell type specific targeted intracellular delivery into muscle of a monoclonal antibody that binds myosin IIb. Mol Immunol. 2003 Mar;39(13):783-9.
Agdeppa ED, Kepe V, Petri A, Satyamurthy N, Liu J, Huang SC, Small GW, Cole GM, Barrio JR. In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer's brain using the positron emission tomography molecular imaging probe [(18)F]FDDNP. Neuroscience. 2003;117(3):723-30.
Gylys KH, Fein JA, Tan AM, Cole GM. Apolipoprotein E enhances uptake of soluble but not aggregated amyloid-beta protein into synaptic terminals. J Neurochem. 2003 Mar;84(6):1442-51.
Morihara T, Chu T, Ubeda O, Beech W, Cole GM. Selective inhibition of Abeta42 production by NSAID R-enantiomers. J Neurochem. 2002 Nov;83(4):1009-12. PMID: 12421374 [PubMed - indexed for MEDLINE]
D'Andrea M, Cole GM, Ard M. The microglial phagocytic role with specific plaque types in the Alzheimer disease brain. Neurobiol. Aging 2004;25:675-83.
Gylys, KH, Fein JA, Cole GM. Synaptic changes in AD: Increased Aß and gliosis is accompanied by shrinkage of terminals and decreased post-synaptic protein expression. Am J. Pathol. 2004;165:1809-1817.
Calon F, Lim G, Yang F, Ubeda O, Rostaing P, Triller A, Salem N Jr, Ashe KH, Frautschy SA, Cole GM. Docosahexaenoic acid protects from dendritic protein loss in an AD mouse model. Neuron 2004;43:633-645.
Zhao L, Teter B, Morihara T, Ambegaokar SS, Ubeda OJ, Frautschy SA, Cole GM. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: Implications for Alzheimer’s disease intervention. J. Neurosci. 2004 Dec 8;24:11120-11126.
Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS,Chen PP, Kayed R, Glabe CG, Frautschy SA, and Cole GM. Curcumin inhibits formation of Aß oligomers and fibrils, binds plaques and reduces amyloid in vivo. J. Biol. Chem. 2005 Feb 18;280(7):5892-901.
Cole GM, Morihara T, Lim GP, Yang F, Begum A and Frautschy SA. NSAID and antioxidant prevention of Alzheimer's disease: Lessons from in vitro and animal models. Annals N. Y. Acad. Sci. 2004;1035:63-84.
Morihara T, Teter B, Yang F, Lim G, Boudinot S, Boudinot D, Frautschy SA and Cole GM. Ibuprofen suppresses interleukin-1ß induction of pro-amyloidgenic a1-antichymotrypsin to ameliorate amyloid pathology in Alzheimer's models. Neuropsychopharmacology 2005 Jan 26; 1-10.
Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, and Cole GM.A diet enriched with the omega-3 fatty acid docosahexaenoic acid (DHA) reduces amyloid burden in an aged Alzheimer mouse model. J. Neurosci. 2005;25(12):3032-40.
John M. Ringman Sally A. Frautschy, Gregory M. Cole, Donna L. Masterman Jeffrey L. Cummings. A Potential Role of the Curry Spice Curcumin in Alzheimer’s Disease . Current Alzheimer Research,2005, 2, 000-000
Calon F, Lim GP, Morihara T, Yang F, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. Related Articles, L Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease. Eur J Neurosci. 2005 Aug;22(3):617-26.
Extracurricular activities Greg likes hiking and walking the dogs, reggae, african music, independent films, and reading literature.