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AMEYLOID VACCINE, AMYLOID REMOVAL MECHANISMS AND SYNAPTI
30 September 2001 - 31 August 2007
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Total Funding: $ 1,285,000
Published data show that beta amyloid vaccination can markedly reduce amyloid burdens, apparently by activating microglia to degrade amyloid. Vaccinations may also prevent certain behavioral deficits. The overall impact on the AD phenotype remains vague. Vaccination might be expected to reduce amyloid but activate microglial inflammatory cytokine production, NADPH oxidase and reactive oxygen species. This may lead to a net decrease or possibly even an increase in oxidative damage and synapse loss. In this proposal, Aim 1 will address unanswered questions about the impact of vaccination at different timepoints on aspects of inflammation while aim 2 will investigate the impact on oxidative damage and synaptic pathology that we have documented in aging APP transgenic mice. Present data suggests that vaccination may not reduce Abeta 40 and vascular amyloid. There is also a real danger that vaccination may induce vascular damage and possibly even hemorrhage. Aim 3 will assess the impact of vaccination on amyloid and soluble Abeta in different compartments, vascular amyloid and vessel damage. Finally, there are unanswered questions about the mechanisms of amyloid reduction induced by vaccination. Available data strongly support an increase in amyloid phagocytosis by microglia, but data on enhanced degradation are inconsistent with some reports showing increases and some showing no change in amyloid degradation. Aim 4 will investigate hypotheses about the mechanisms involved in vaccine induced amyloid reductions. If successful, these experiments would be expected to lead to small molecule approaches to mitigate potential harmful effects of vaccination and to conceivably enhance amyloid removal.
11 Resulting Publications
Jeffrey A Fein; Sophie Sokolow; Carol A Miller; Harry V Vinters; Fusheng Yang; Gregory M Cole; Karen Hoppens GylysThe American journal of pathology 2008;172(6):1683-92.
Qiu-Lan Ma; Marni E Harris-White; Oliver J Ubeda; Mychica Simmons; Walter Beech; Giselle P Lim; Bruce Teter; Sally A Frautschy; Greg M ColeJournal of neurochemistry 2007;103(4):1594-607.
Qiu-Lan Ma; Giselle P Lim; Marni E Harris-White; Fusheng Yang; Surendra S Ambegaokar; Oliver J Ubeda; Charles G Glabe; Bruce Teter; Sally A Frautschy; Greg M ColeJournal of neuroscience research 2006;83(3):374-84.
Lixia Zhao; Qiu-Lan Ma; Frédéric Calon; Marni E Harris-White; Fusheng Yang; Giselle P Lim; Takashi Morihara; Oliver J Ubeda; Surendra Ambegaokar; James E Hansen; et al.Nature neuroscience 2006;9(2):234-42.
Greg M Cole; Giselle P Lim; Fusheng Yang; Bruce Teter; Aynun Begum; Qiulan Ma; Marni E Harris-White; Sally A FrautschyNeurobiology of aging 2005;26 Suppl 1():133-6.
Frédéric Calon; Giselle P Lim; Takashi Morihara; Fusheng Yang; Oliver Ubeda; Norman Salem; Sally A Frautschy; Greg M ColeThe European journal of neuroscience 2005;22(3):617-26.
Takashi Morihara; Bruce Teter; Fusheng Yang; Giselle P Lim; Sally Boudinot; F Douglas Boudinot; Sally A Frautschy; Greg M ColeNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2005;30(6):1111-20.
John M Ringman; Sally A Frautschy; Gregory M Cole; Donna L Masterman; Jeffrey L CummingsCurrent Alzheimer research 2005;2(2):131-6.
Fusheng Yang; Giselle P Lim; Aynun N Begum; Oliver J Ubeda; Mychica R Simmons; Surendra S Ambegaokar; Pingping P Chen; Rakez Kayed; Charles G Glabe; Sally A Frautschy; et al.The Journal of biological chemistry 2005;280(7):5892-901.
Greg M Cole; Takashi Morihara; Giselle P Lim; Fusheng Yang; Aynun Begum; Sally A FrautschyAnnals of the New York Academy of Sciences 2004;1035():68-84.
Frédéric Calon; Giselle P Lim; Fusheng Yang; Takashi Morihara; Bruce Teter; Oliver Ubeda; Phillippe Rostaing; Antoine Triller; Norman Salem; Karen H Ashe; et al.Neuron 2004;43(5):633-45.
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Golde, Todd E
1 September 2002 - 31 August 2006
NATIONAL INSTITUTE ON AGING
Total Funding: $ 706,819
Davies, Peter P
1 March 2006 - 28 February 2011
NATIONAL INSTITUTE OF MENTAL HEALTH
Total Funding: $ 4,531,594
Cole, Gregory M
1 September 2005 - 31 August 2009
NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE
Total Funding: $ 1,072,290
Sang-Ho Choi; Saba Aid; Luca Caracciolo; S Sakura Minami; Takako Niikura; Yasuji Matsuoka; R Scott Turner; Mark P Mattson; Francesca BosettiJournal of neurochemistry 2013;124(1):59-68.
Mark P Mattson; Sic L ChanScience (New York, N.Y.) 2003;301(5641):1847-9.
Dale SchenkNature reviews. Neuroscience 2002;3(10):824-8.
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