Fagan Laboratory

Anne M. Fagan, PhD

faganLabGroupPhotoAnne Fagan is a Research Associate Professor of Neurology

In 1995, Anne was recruited by Dr. David Holtzman, a long-time colleague, to gain training in Alzheimer’s Disease (AD) and help establish his lab at Washington University School of Medicine, and subsequently received her faculty appointment in the Department of Neurology in 1997.

She maintains her close collaborations with David Holtzman investigating the pathobiology of AD. Anne is a member of the Society for Neuroscience, the St. Louis Chapter of Women in Neuroscience, and the Academic Women’s Network at Washington University. She is a Washington University Alzheimer’s Disease Research Center Investigator, a faculty member of the Hope Center for Neurological Disorders, and the 2006 recipient of the Alzheimer’s Disease Neuroimaging Award (New Investigator) awarded by the Alzheimer’s Association.

For the past ten years Anne has been investigating the mechanism(s) by which the E4 isoform of apolipoprotein E (apoE) is a risk factor for AD. Her multidisciplinary approach, utilizing biochemical and cell biological experiments coupled with analysis of in vivo transgenic mouse models of AD, has been instrumental in defining an important role for apoE in the metabolism of amyloid-b (Abeta), the protein that accumulates and forms plaques in the AD brain. Over the past five years, her interests have expanded into the AD biomarker field, with publications describing CSF lipoprotein-associated Abeta and sulfatide measures as candidate biomarkers of preclinical and early stage AD. Anne is a co-investigator on the biomarkers portion of a large, long-standing Program Project through the Washington University ADRC investigating brain and cognitive health during healthy aging and dementia. She is also the Principal Investigator of the biomarkers section of a newly funded Program Project (Adult Children Study) designed to identify antecedent biomarkers of AD (i.e., biomarkers to detect AD prior to clinical symptoms). In addition, Anne is supervising efforts to develop a relational database of existing antecedent biomarker studies and to coordinate development of common protocols for collection and analysis of biological samples and cognitive assessment.

anneFaganContact the Fagan-Niven Lab

E-mail: fagana@neuro.wustl.edu
Phone: (314) 362-3453 – office; (314) 747-0286 – lab
Fax: (314) 362-2244
Mailing address:
Washington University School of Medicine
Department of Neurology
660 South Euclid
Campus Box 8111
St. Louis, MO 63110

Publications

  1. Fagan AM, Bu G, Sun Y, Daugherty A, Holtzman DH. Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein (LRP). J. Biol. Chem. 1996; 271:30121-30125.
  2. AM, Murphy BA, Patel SN, Kilbridge JF, Mobley WC, Bu G, Holtzman DM. Evidence for normal aging of the septo-hippocampal cholinergic system in apoE (-/-) mice but impaired clearance of axonal degeneration products following injury, Exp. Neurol. 1998; 151:314-325.
  3. Holtzman DM, Bales KR, Wu S, Bhat P, Parsadanian M, Fagan AM, Chang LK, Sun Y, Paul SM. Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer’s disease, J. Clin. Invest. 1999; 103:R15-R21.
  4. Fagan AM, Younkin JH, Morris JC, Fryer JD, Cole TG, Younkin SG, Holtzman DH. Differences in the Ab40/Ab42 ratio associated with cerebrospinal fluid lipoproteins as a function of apolipoprotein E genotype, Ann. Neurol. 2000; 48:201-210.
  5. AM, Holtzman DM, Munson G, Mathur T, Schneider D, Chang L, Getz GS, Reardon CA, Lukens J, Shah JA, LaDu MJ, Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-/-) and human apoE transgenic mice, J. Biol. Chem., 2000; 274:30001-30007.
  6. DM, Fagan AM, Mackey B, Tenkova T, Sartorius L, Paul SM, Bales K, Hsiao Ash K, Irizarry MC, Hyman BT. ApoE facilitates neuritic and cerebrovascular plaque formation in an Alzheimer’s disease model, Ann. Neurol.. 2000; 47:739-747.
  7. AM, Holtzman DM. Astrocyte lipoproteins, effects of apoE on neuronal functions, and role of apoE in amyloid-b deposition in vivo, Microsc. Res. Tech. 2000; 50:297-304
  8. AM, Watson M, Parsadanian M, Bales KR, Paul SM, Holtzman DH. Human and Murine apoE markedly influenced Ab metabolism before and after plaque formation in a mouse model of Alzheimer’s disase, Neurobiol. Dis. 2002; 9:305-318.
  9. X, Fagan AM, Cheng H, Morris JC, Xiong C and Holtzman DM. Cerebrospinal fluid sulfatide is decreased in subjects with incipient dementia, Ann. Neurol., 2003, 54:115-118.
  10. X, Cheng H, Fryer JD, Fagan AM, Holtzman DM Novel role for apolipoprotein E in the central nervous system: Modulation of sulfatide content, J. Biol. Chem., 2003; 278: 8043-8051.
  11. AM, Christopher E, Taylor JW, Parsadanian M, Spinner M, Watson M, Fryer JD, Wahrle S, Bales KR, Paul SM, Holtzman DM. ApoAI deficiency results in marked reductions in plasma cholesterol but no alterations in amyloid-b pathology in a mouse model of Alzheimer’s disease-like cerebral amyloidosis, Am. J. Pathol., 2004, 165:1413-1422.
  12. M, Fryer JD, Sullivan PM, Christopher EA, Wahrle SE, DeMattos RB, O’Dell MA, Fagan AM, Lashuel HA, Walz T, Asai K, Holtzman DM. Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-beta, Neurobiol. Dis., 2005, 19:66-76.
  13. JR, Deane R, Fagan AM, Spinner ML, Parsadanian M, Finn MB, Jiang H, Prior JL, Sagare A, Bales KR, Paul SM, Zlokovic BV, Piwnica-Worms D, Holtzman DM. P-glycoprotein deficiency at the blood-brain barrier increases amyloid-b deposition in an Alzheimer’s disease mouse model, J. Clin. Invest., 2005, in press.
  14. AM, Csernansky CA, Morris JC, Holtzman DM. The search for antecedent biomarkers of Alzheimer’s disease, Journal of Alzheimer’s Disease, 2005, 8(4):347-58.
  15. Y, Townsend R, Fagan AM, Holtzman DM. Comparative proteomics analysis of intra- and inter-individual variation in human cerebrospinal fluid, Mol and Cell Proteomics, 2005,4:2000-2009.
  16. AM, Mintun MA, Mach RH, Lee S-Y, Dence CS, Shah AR, LaRossa G, Spinner ML, Klunk WE, Mathis CA, DeKosky ST, Morris JC, Holtzman DM Inverse relation between in vivo amyloid imaging load and CSF Ab42 in humans, Annals of Neurology, 2006, 59:512-519.
  17. RE, Shah A, Fagan AM, Schwetye KE, Parsadanian M, Schulman RN, Finn MB, Holtzman DM Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer’s disease, Neurobiol Dis, 2006, 24:506-515.
  18. JG, Dong H, Fagan AM, Wang L, Xiong C, Holtzman DM, and Morris JC. Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia, Am J Psychiatry, 2006, 163: 2164-9.
  19. AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM Cerebrospinal fluid tau/b-amyloid42 ratio as a prediction of cognitive decline in nondemented older adults, Arch Neurol, 2007, in press.
  20. JSK, Jacquart S, Chakraverty S, Wang J, Mayo K, Mintun M, Fagan AM, Holtzman DM, Morris JC, Goate AM. Use of cerebrospinal fluid amyloid-β levels as an endophenotype identifies a PSEN1 mutation causing Alzheimer’s disease in a late-onset family. Ann Neurol, 2007, in press.
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Sushi Sathyan, Research Patient Coordinator Aarti Shaw – Senior Technician Richard Perrin