Anne M. Fagan, PhD
In 1995, Anne was recruited to Washington University School of Medicine by Dr. David Holtzman, a long-time colleague, to gain training in Alzheimer's Disease (AD), and subsequently received her faculty appointment in the Department of Neurology in 1997.
In her post-doctoral and early faculty yeyars Anne investigated 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, was instrumental in defining an important role for apoE in the metabolism of amyloid-ï™¢ (Aï™¢), the protein that accumulates and forms plaques in the AD brain. Over the past twelve years, her interests have expanded into the AD biomarker field, with publications describing the utility of various CSF measures as diagnostic and prognostic biomarkers of preclinical and early stage AD.
Anne is a co-investigator on the fluid biomarkers portion of a large, long-standing Program Project through the Washington University Alzheimer's Disease Research Center (ADRC) investigating brain and cognitive health during healthy aging and dementia (HASD). She is also the Principal Investigator of the fluid biomarkers section of the Adult Children Study (ACS) designed to identify antecedent biomarkers of AD. She is the Biomarker Core director for both the ACS as well as a new international, multicenter study ("Dominantly Inherited Alzheimer Network", DIAN) designed to identify antecedent fluid biomarkers of AD in families harboring autosomal-dominant AD gene mutations. She is a member of the Resource Allocation Committee for the Alzheimer's Disease Neuroimaging Initiative (ADNI) and a member of the Working Group on Preclinical AD Biomarkers sponsored by the NIA in collaboration with the Alzheimer's Association. She recently supervised efforts to design a web-based relational database (currently hosted by Alzforum) that was made publically available to colleagues studying antecedent biomarkers of AD. She continues to be involved in updating the public face of this database, permitting AD investigators to "advertise" the details of their biomarker studies in order to foster collaboration and increased productivity in the field of antecedent biomarkers of AD.
Anne received her B.A. in Psychobiology from Wellesley College in 1984 and her Ph.D. in Neuroscience from the University of California San Diego in 1992 where she investigated the role of trophic factors in injury-induced neuronal plasticity under the mentoring of Dr. Fred "Rusty" Gage. She expanded upon this theme during her post-doctoral training at Bristol-Myers Squibb Pharmaceutical Research Institute investigating the role of trophic factor interactions in neuronal development. 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.
Publications (since 2005)
Morikawa 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.
Cirrito 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-ï™¢ deposition in an Alzheimer's disease mouse model, J. Clin. Invest., 2005, 115:3285-3290.
Hu Y, Townsend R, Fagan AM, Holtzman DM. Comparative proteomics analysis of intra- and inter-individual variation in human cerebrospinal fluid, Mol. Cell. Proteomics, 2005, 4:2000-2009.
Fagan 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 Aï™¢42 in humans, Ann. Neurol., 2006, 59:512-519.
Fagan AM, Csernansky CA, Morris JC, Holtzman DM. The search for antecedent biomarkers of Alzheimer's disease, J. Alzheimer's Dis., 2005, 8:347-358.
Csernansky 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.
Kauwe 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, 61(5):446-53.
Wahrle SE, Shah AR, Fagan AM, Smemo S, Kauwe JSK, Grupe A, Hinrichs A, Mayo K, Jiang H, Thal LJ, Goate AM, Holtzman DM. Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1 polymorphisms. Mol. Neurodegen., 2007, Apr 12;2:7.
Hu Y, Hosseini A, Kauwe JSK, Gross J, Cairns NJ, Goate AM, Fagan AM, Townsend RR, Holtzman DM Identification and validation of novel CSF biomarkers for early stages of Alzheimer's disease. Proteomics - Clin. Appl., 2007, 1:1373-1384.
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? Rejuv. Res., 2008, 11: 321-332. Accepted prior to April 7, 2008.
Kauwe JS, Cruchaga C, Mayo K, Fenoglio C, Bertelsen S, Nowotny P, Galimberti D, Scarpini E, Morris JC, Fagan AM, Holtzman DM, Goate AM. Variation in MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition. PNAS, 2008 105:8050-4. PMCID: PMC2430357
Fagan AM, Head, D, Shah AR, Marcus D, Mintun M, Morris JC, Holtzman DM. Decreased cerebrospinal fluid Aβ42 correlates with brain atrophy in cognitively normal elderly. Ann Neurol 2009, 65:176-183. PMCID: PMC2763631
Okereke OI, Xia W, Irizarry MC, Sun X, Qiu WQ, Fagan AM, Mehta PD, Hyman BT, Selkoe DJ, Grodstein F. Performance characteristics of plasma amyloid-beta 40 and 42 assays. J Alzheimers Dis., 2009,16:277-85. PMCID: PMC2737811
Kauwe JS, Wang J, Mayo K, Morris JC, Fagan AM, Holtzman DM, Goate AM. Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta. Neurogenetics. 2009,10:13-7. PMCID: PMC2726757
Craig-Schapiro R, Fagan AM, Holtzman DM. Biomarkers of Alzheimer's disease. Neurobiol Dis., 2009, 35:128-40. PMCID: PMC2747727
Britschgi M, Olin CO, Johns HT, Takeda-Uchimura Y, LeMieux M, Rufibach K, Rajadas J, Zhang H, Tomooka B, Robinson WH, Clark CM, Fagan AM, Galasko DG, Holtzman DM, Jutel M, Kaye JA, Lemere CA, Leszek J, Li G, Peskind ER, Quinn JF, Yesavage JA, Ghiso J., and Wyss-Coray T. Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease. PNAS, 2009, 106:12145-50. PMCID: PMC2715538
Clifford DB, Fagan AM, Holtzman DM, Morris, JC, Teshome M, Shah AR, Kauwe JSK. CSF biomarkers of Alzheimer's Disease in HIV associated neurological disease. Neurology, 2009, 73:1982-87. PMCID: PMC2790234
Duchek JM, Balota DA, Tse CS, Holtzman DM, Fagan AM, Goate AM. The utility of intraindividual variability in selective attention tasks as an early marker for Alzheimer's disease. Neuropsychology, 2009, 23:746-58. PMCID: PMC2779520
Morris JC, Roe CM, Xiong C, Fagan AM, Goate Am, Holtzman DM, Mintun MA. APOE predicts Aβ but not tau Alzheimer's pathology in cognitively normal aging, Ann Neurol, 2010, 67:122-31. PMCID: PMC2830375
Cairns NJ, Ikonomovic MD, Benzinger T, Storandt M, Fagan AM, Shah AR, Taylor-Reinwald L, Carter D, Felton A, Holtzman DM, Mintun MA, Klunk WE, Morris JC. Absence of Pittsburgh Compound B detection of cerebral amyloid beta in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease, Arch Neurol, 2009, 66:1557-62. PMCID: PMC2796200
Morris JC, Roe CM, Grant EA, Head D, Storandt M, Goate AM, Fagan AM, Holtzman DM, Mintun MA. PIB imaging predicts progression from cognitively normal to symptomatic Alzheimer's disease, Arch Neurol, 2009, 66:1469-75. PMCID: PMC2798814
Perrin RJ, Fagan AM, Holtzman DM. Multimodal techniques for diagnosis and prognosis of Alzheimer's disease, Nature, 2009, 461:916-22 PMCID: PMC2810658
Fagan AM, Mintun MA, Shah AR, Aldea P, Roe CM, Mach RH, Marcus D, Morris JC, Holtzman DM. Cerebrospinal fluid tau and ptau181 increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer's disease. EMBO Mol Med, 2009, 1:371-80. PMCID: PMC2806678
Fagan AM and Holtzman DM. CSF biomarkers of Alzheimer's disease. Future Med, 2010, 4:51-63. [PMC Journal - In process]
Ances BM, Christensen JJ, Teshome M, Taylor J, Xiong C, Aldea P, Fagan AM, Holtzman DM, Morris JC, Mintun MA, Clifford DB. Cognitively unimpaired HIV+ participants do not have increased 11C-PiB: A case control study. Neurology, 2010, in press. [PMC Journal - In process]
Kauwe JSK, Cruchaga C, Bertelsen S, Mayo K, Latu W, Nowotny P, Hinrichs AL, Fagan AM, Holtzman DM, ADNI and Goate AM. Validating predicted biological effects of Alzheimer's disease associated SNPs using CSF biomarker levels. J Alzheimer Dis, 2010, in press.
© 2006-2012 Washington University School of Medicine