POSITION TITLE:Associate Professor of Neurology, Harvard
INSTITUTION AND LOCATION
FIELD OF STUDY
Mount Holyoke College, South Hadley, MA
SUNY at Albany, NY
Boston University School of Medicine, Boston, MA
A. Positions and Honors:
1980-1983 Graduate Student, SUNY at Albany, NY (Biology)
1980-1983 Graduate Teaching Assistant, SUNY at Albany (Biology)
1983-1984 Laboratory Technician, SUNY at Albany
1986-1989 Staff Research Associate, University of California, San Diego, School of Medicine, San Diego, CA (Neuroscience)
1989 Consultant, American Heart Association of San Diego, CA
1990-1995 Senior Technical Research Assistant, Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, MA
1991-1995 Graduate Student, Doctoral Program in Pathology, Boston University School of Medicine
1995-1996 Research Fellow in Neurology, Harvard Medical School, Boston, MA
1995-1996 Research Fellow in Medicine, Department of Neurology, Brigham and Women's Hospital
1996-1997 Instructor in Neurology, Harvard Medical School
1996- Associate Neuroscientist, Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital
1997-2004 Assistant Professor in Neurology, Harvard Medical School
1998-1999 Consultant, Biogen Inc., Boston, MA
2004- Associate Professor of Neurology, Harvard Medical School
1980 Magna Cum Laude, Mount Holyoke College
1980 Sigma Xi, Phi Beta Kappa
1991-1993 George O'Neill Fund at the Foundation for Neurologic Diseases - For graduate student support
1992-1995 Graduate Scholarship, Boston University School of Medicine (Pathology) 1997 Leadership Award, Children¡¯s Hospital Volunteer Program
1997 Premio Alejandro Angel Escobar en Ciencias (Alejandro Angel Escobar Prize in Sciences), Bogota, Colombia
2003, 2007 Partners in Excellence Award, Brigham and Women¡¯s Hospital, Boston, MA
1996- Society for Neuroscience
1996- American Association for the Advancement of Science
2001- New York Academy of Sciences
2005- AFAR National Scientific Advisory Council
2007- International AD/PD Meeting Scientific Advisory Board
2007- Alzforum Scientific Advisory Board
B. B. Selected peer-review publications (out of a total of 60):
Murphey RK, Lemere CA. Competition controls the growth of an identified axonal arborization. Science 1984;224: 1352-1355.
Haass C, Lemere CA, Capell A, Citron M, Seubert P, Schenk D, Lannfelt L, Selkoe DJ. b-Secretase cleavage of b-amyloid precursor protein with the Swedish mutation occurs within the secretory pathway after the trans-Golgi network. Nature Med 1995; 1 (12): 1291-1296.
Lemere CA, Blusztajn J K, Yamaguchi H, Wisniewski T, Saido T C, Selkoe D J. Sequence of deposition of heterogeneous amyloid b-peptides and Apo E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol Disease 1996; 3 (1): 16-32.
Lemere CA, Lopera F, Kosik KS, Lendon CL, Ossa J, Saido TC, Yamaguchi H, Ruiz A, Martinez A, Madrigal L, Hincapie L, Arango-LJC, Anthony DC, Koo E, Goate A, Selkoe DJ, Arango-VJC. The E280A presenilin 1 Alzheimer mutation produces increased Ab42 deposition and severe cerebellar pathology. Nature Med 1996; 2: 1146-1150.
Lemere CA, Grenfell TJ, Selkoe DJ. The “AMY” antigen co-occurs with Ab and follows its deposition in the amyloid plaques of Alzheimer’s disease and Down syndrome. Am J Pathol 1999; 155: 29-37.
Stoltzner SE, Grenfell TJ, Mori C, Wisniewski T, Wisniewski K, Selkoe DJ, Lemere CA. Temporal sequence of complement proteins in AD plaques in Down syndrome brain. Am J Pathol 2000;156:489-499.
Lemere CA, Maron R, Spooner ET, Grenfell TG, Mori C, Desai R, Hancock WW, Weiner HL, Selkoe DJ. Nasal Ab treatment induces anti-Ab antibody production and decreases cerebral amyloid burden in PDAPP mice. Annals of the New York Academy of Sciences 2000; 920: 328-331.
Weiner HL, Lemere CA, Maron R, Spooner ET, Grenfell TJ, Mori C, Issazadeh S, Hancock WW, Selkoe DJ. Nasal administration of amyloid b-peptide decreases cerebral amyloid burden in a mouse model of Alzheimer’s disease. Annals of Neurology 2000; 48, 567-579.
Matsuoka Y, Picciano M, Malester B, LaFrancois J, Zehr C, Daeschner JM, Olshowka JA, Fonseca MI, O'Banion KM, Tenner AJ, Lemere CA, Duff K. Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer's disease. Am J Pathol 2001; 158: 1345-1354.
Lemere CA, Maron R, Selkoe DJ, Weiner, HL. Nasal vaccination with b-amyloid peptide for the treatment of Alzheimer's disease. DNA and Cell Biology 2001; 20: 705-711.
Mori C, Spooner ET, Wisniewski KE, Wisniewski TM, Yamaguchi H, Saido T, Tolan DR, Selkoe DJ, Lemere CA. Intraneuronal Ab42 accumulation in Down syndrome brain. Amyloid J Protein Fold Disord2002;9:88-102.
Spooner ET, Desai RV, Mori C, Leverone J, Lemere CA. The generation and characterization of potentially therapeutic Ab antibodies in mice: Differences according to strain and immunization protocol. Vaccine 2002; 21: 290-297.
Lemere CA, Spooner ET, Leverone JF, Mori C, Clements, JD. Intranasal immunotherapy for the treatment of Alzheimer's disease: E. coli LT and LT(R192G) as mucosal adjuvants. Neurobiol Aging 2002; 23:991-1000.
Matsuoka Y, Saito M, LaFrancois J, Saito M, Gaynor K, Olm V, Wang L, Casey E, Lu Y, Shiratori C, Lemere C, Duff K. Novel therapeutic approach for the treatment of Alzheimer's disease by peripheral administration of agents with an affinity to b-amyloid.. J Neurosci 2002; 23(1): 29-33.
Lemere CA, Seabrook TJ, Iglesias M, Mori C, Leverone JF, Spooner ET. Modulating Amyloid-b levels by immunotherapy: A potential therapeutic strategy for the prevention and treatment of Alzheimer's disease. In: Saido T(ed.), Amyloid-Beta Metabolism and Alzheimer's Disease. Landes Biosci, Eureka.com,2002:145-161.
Leverone JF, Spooner ET, Lehman H, Clements JD, Lemere CA. A1-15 is less immunogenic than AI I1-40/42 for intranasal immunization of WT mice but may be effective for "boosting". Vaccine 2003; 21: 2197-2206.
Lemere, CA, Spooner ET, Leverone JF, Mori C, Iglesias M, Bloom JK, Seabrook TJ. Amyloid-b immunization in Alzheimer's disease transgenic mouse models and wildtype mice. Neurochem Res, 2003; 28: 1017-1027.
Lemere CA, Spooner ET, LaFrancois J, Malester B, Mori C, Leverone JF, Matsuoka Y, DeMattos RB, Holtzman DM, Clements JD , Selkoe DJ, Duff KE. Evidence for peripheral clearance of cerebral Ab protein following chronic, active Ab immunization in PSAPP mice. Neurobiology of Disease, 2003; 14:10-18
Lemere CA, Beierschmitt A, Iglesias M, Spooner ET, Bloom JK, Leverone JF, Zheng, JB, Seabrook TJ, Louard D, Li D, Selkoe DJ, Palmour RM, Ervin FR. Alzheimer’s disease Ab vaccine reduces CNS Ab levels in a non-human primate, the Caribbean vervet. Am J Pathol 2004; 165: 283-297.
Seabrook TJ, Bloom JK, Iglesias M, Spooner ET, Walsh DM, Lemere CA. Species-specific immune response to immunization with human vs rodent Ab peptide. Neurobiol Aging 2004; 25: 1141-1151.
Seabrook TJ, Iglesias M, Bloom JK, Spooner ET, Lemere CA. Differences in the immune response to long term Ab vaccination in C57BL/6 and B6D2D1 mice. Vaccine 2004; 22: 4075-4083.
Maier M, Seabrook TJ, Lemere CA. Modulation of the humoral and cellular immune response in Aß immunotherapy by the adjuvants Monophosphoryl Lipid A (MPL), Cholera Toxin B subunit (CTB) and E. coli enterotoxin LT(R192G). Vaccine 2005; 23:5149-5159.
Maier M, Seabrook TJ, Lemere CA. Developing novel immunogens for an effective, safe Alzheimer’s disease vaccine. Neurodegen Dis 2005; 2: 267-272.
Klyubin I, Walsh DM, Lemere CA, Cullen WK, Shankar GM, Betts V, Spooner ET, Jiang L, Anwyl R, Selkoe DJ, Rowan MJ. Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nature Med 2005; 11(5): 556-561.
Lemere CA, Maier M, Jiang L, Peng Y, Seabrook TJ. Amyloid ß immunotherapy for the prevention and treatment of Alzheimer’s disease: Lessons from mice, monkeys and humans. Rejuvenation Res 2006;9:77-84.
Seabrook TJ, Jiang L, Maier M, Lemere CA. Minocycline affects microglial activation, Aß deposition and behavior in APP-tg mice. Glia 2006; 53:776-782.
Maier M, Seabrook TJ, Lazo ND, Jiang L, Das P, Janus C, Lemere CA. Short Aß immunogens reduce cerebral Aß load and learning deficits in an Alzheimer’s disease mouse model in the absence of an Aß-specific cellular immune response. J Neurosci 2006; 26(18):4717-4728.
Seabrook TJ, Jiang L, Thomas KE, Lemere CA. Boosting with intranasal dendrimeric Aß1-15 but not Aß1-15 peptide leads to an effective immune response following a single injection of Aß1-40/42 in APP-tg mice. J Neuroinflammation 2006; Jun 5;3(1):14.
Lui K, Solano I, Mann D, Lemere C, Merken M, Trojanowski JQ, Lee V M-Y. Characterization of Aß11-40/42 peptide deposition in Alzheimer's disease and young Down's syndrome brains: Implication of the N-terminally truncated Aß species in the pathogenesis of Alzheimer's disease. Acta Neuropathol 2006; 112(2):163-164.
Peng Y, Jiang L, Lee D Y-W, Schachter SC, Ma Z, Lemere CA. Effects of Huperzine A on amyloid precursor protein processing and Aß generation in human embryonic kidney 293 APP Swedish mutant cells. J Neurosci Res 2006; 84(4):903-911.
Seabrook TJ, Thomas K, Jiang L, Bloom J, Spooner E, Maier M, Bitan G, Lemere CA. Dendrimeric Abeta1-15 is an effective immunogen in wildtype and APP-tg mice. Neurobiol Aging 2007; 28(6):813-823.
Lemere CA. A Beneficial Role For IL-1ß in Alzheimer Disease? J Clin Invest 2007; 117(6):1483-1485.
Lemere CA, Maier M, Peng Y, Jiang L, Seabrook TJ. Novel Aß Immunogens: Is Shorter Better? Current Alzheimer’s Research 2007; 4:427-436.
He P, Zhong Z, Lindholm K, Berning L, Lee W, Lemere C, Staufenbiel M, Li R, Shen Y. Deletion of tumor necrosis factor death receptor inhibits amyloid ß generation and prevents learning and memory deficits in Alzheimer's mice. J Cell Biol 2007; 178(5):829-841.
Peng Y, Lee DY-W, Jiang L, Ma Z, Schachter SC, Lemere CA. Huperzine A regulates amyloid precursor protein processing via protein kinase C and MAP kinase pathways in SK-N-SH cells over-expressing wild type human APP695. Neuroscience 2007; 150(2):385-395.
Kondo Y, Lemere CA, Seabrook TJ. Osteopetrotic (op/op) mice have reduced microglia, no Abeta deposition, and no changes in dopaminergic neurons. J Neuroinflammation 2007; 4:31 doi:10.1186/1742-2094-4-31.
Lemere, CA. Molecular Mechanisms of Neurodegeneration - Abcam Meeting, Antigua, Eastern Caribbean, IDDB Meeting Report 2007 3-6 Dec (www.iddb.com).
Lemere CA, Oh J, Stanish HA, Peng Y, Pepivani I, Fagan AM, Yamaguchi H, Westmoreland SV, Mansfield KG. Cerebral Amyloid-Beta Protein Accumulation With Aging in Cotton-Top Tamarins: A Model of Early Alzheimer's Disease? Rejuvenation Res 2008; in press.
Klyubin I, Betts V, Welzel A, Blennow K, Zetterberg, H, Wallin A, Lemere CA, Cullen WK, Peng Y, Wisniewski T, Selkoe DJ, Anwyl R, Walsh DM, Rowan MJ. Aß dimer-containing human cerebral spinal fluid disrupts synaptic plasticity: prevention by systemic passive immunization. J Neurosci 2008; in press.
Maier M, Peng Y, Jiang L, Seabrook TJ, Carroll MC, Lemere CA. Complement C3-deficiency leads to accelerated Aß plaque deposition and neurodegeneration, and modulation of the microglia/macrophage phenotype in APP transgenic mice. J Neurosci 2008; in press.
C. Research Support:
Corporate Sponsored Research Project (PI) 1/19/05 – 1/18/07 (no cost extension until 1/31/08)
Elan Pharmaceutical Corp. /Wyeth
Active Abeta Immunization in Vervet Primates
The goal of this project is to test a novel, active Ab vaccine in a non-human primate model.
Alzheimer's Association IIRG (PI) 11/1/06 – 10/31/09
Protective Effects of Chronic L-NBP Treatment in an AD Mouse Model
The goal of this project is to determine the neuroprotective and therapeutic properties of a synthetic compound derived from celery seed extract, L-NBP, on pathogenesis and cognitive deficits in an AD mouse model.
2R01 AG20159-06 Lemere (PI) 2/1/07 – 1/31/12
National Institute on Aging
Mucosal Ab Vaccination: Modulating the Immune Response
The major goals of this project are: 1. To optimize Ab immunization protocols in wildtype mice, 2. To implement the optimal protocol(s) to vaccinate APP, PSAPP and PS1 transgenic mice, and 3. To crossbreed APP transgenic mice with complement-deficient mice to search for possible mechanisms of how the Ab vaccine leads to decreased cerebral Aß levels.
Anonymous Foundation Grant Lemere (PI) 8/15/06 – 8/14/08
Characterization of Aging in Caribbean Vervets: A Potential Model for Testing Alzheimer’s Disease Therapeutics
The major goal of this study is to characterize AD biomarkers in plasma and CSF and perform longitudinal cognitive testing in a cohort of middle-aged and aged living monkeys. In addition, we will perform in-depth neuropathological analysis of archived brain tissue and will set up a protocol for prospective tissue collection and analysis.
R01 AG20159 Lemere (PI) 9/30/01 – 7/31/06
National Institute on Aging
Mucosal Ab Vaccination: Modulating the Immune Response
The major goals of this project are to improve safety and efficacy of a vaccine for AD by: 1. Testing novel short Aß immunogens that target Aß B cell epitopes while avoiding Aß T cell epitopes via 4 routes of administration in wildtype mice, 2. Testing the best immunogens in young (prevention) and old (therapeutic) APP tg mice, and 3. Determining the roles of complement C3 and its receptor C3R (Mac-1) in Aß clearance in the presence or absence of Aß antibodies.
IIRG-00-2062 Lemere (PI) 9/1/00 – 8/31/04
The Role of Antibodies to Amyloid b-Protein in Preventing and Treating Alzheimer’s Disease
The major goal of this project was to confirm Ab immunization results in PDAPP mice, test the effects of antibodies in phagocytosis of Ab by cultured microglia, and to screen serum samples from human centenarians for anti-Ab antibodies.
P50 NS28275 Lansbury (Program Director) 9/30/99 – 7/31/04
National Institute of Neurological Disorders and Stroke
Morris K. Udall Parkinson’s Disease Research Center: Familial Parkinson’s Disease: Clues to Pathogenesis
CORE A Frosch (PI)
The aims of this Center proposal were to investigate the role of I I-synuclein, Parkin and ubiquitin
C-hydrolase in Parkinson’s disease etiology. The goal of CORE A was to provide neuropathological, histological and immunohistochemical services for examination of I I-synuclein, Parkin and ubiquitin C-hydrolase in human brain and tg mouse brains.
Role on Core A: Co-Investigator