Anne Fagan, PhD
Professor of Neurology
Cerebrospinal fluid and plasma biomarkers of early stage Alzheimer’s Disease Read More
|Lab Phone:||(314) 362-3453|
|Lab Location:||BJC IH 9305|
|Keywords:||Alzheimer's disease, biomarkers, cerebrospinal fluid, amyloid, tau, ELISA, proteomics|
Cerebrospinal fluid and plasma biomarkers of early stage Alzheimer’s Disease
Alzheimer disease (AD), the most common cause of dementia in the elderly, is a progressive and fatal neurodegenerative disorder. AD currently affects ~10.6 million people in the U.S. and Europe, with numbers expected to double every 20 years unless effective disease-modifying treatments are developed (http://www.alz.org). Suboptimal clinical diagnostic accuracy and the existence of a long preclinical phase during which the hallmark pathologies (amyloid plaques, neurofibrillary tangles and neuronal injury/death) develop prior to the appearance of clinical symptoms has propelled efforts to identify biomarkers to aid disease diagnosis and prognosis, especially during the preclinical and early clinical stages. Individuals in the preclinical stage are currently receiving intense focus as a targeted population for AD secondary prevention trials. In such trials, biomarkers are being used for subject enrollment, proof of therapeutic target engagement and as surrogates for assessing downstream effects on disease pathology. Thus, it is critical to elucidate the trajectories of biomarker changes during the natural course of the disease, especially during this dynamic preclinical phase.
Dr. Fagan received a BA (Psychobiology) from Wellesley College in 1984 and PhD (Neuroscience) from University of California, San Diego in 1992 under the mentorship of Dr. Fred “Rusty” Gage. In 1995 she joined the lab of Dr. David Holtzman at Washington University, and is currently a Research Professor in the Department of Neurology, a Knight Alzheimer’s Disease Research Center (KADRC) Investigator and faculty member of the Hope Center for Neurological Disorders. Dr. Fagan’s foray into biomarkers began with a study investigating the influence of APOE genotype (the strongest genetic risk factor for AD) on CSF lipoproteins in cognitively normal elders. Together with Dr. John Morris, the Director of the KADRC, and other ADRC colleagues, they expanded their CSF studies and embarked upon visionary, longitudinal studies investigating the potential of a variety of fluid (and neuroimaging) measures as biomarkers of preclinical (antecedent) AD pathology. Dr. Fagan is co-investigator on the fluid biomarkers portion of a long-standing Program Project investigating healthy aging and dementia (HASD), and the Biomarker Core Leader and PI of the biomarker portion of the Adult Children Study (ACS) evaluating longitudinal biomarker patterns in middle-aged individuals at different risk for AD based on family history. She also serves as the Biomarker Core Leader for the Dominantly Inherited Alzheimer Network (DIAN), a study designed to identify antecedent fluid biomarkers of AD in families harboring autosomal-dominant AD gene mutations, and the associated DIAN Trial Unit (DIAN TU), the first AD secondary prevention trial. Dr. Fagan is a member of the Society for Neuroscience, the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART), the St. Louis Chapter of Women in Neuroscience, and the Academic Women’s Network at Washington University. She is the 2006 recipient of the Alzheimer’s Disease Neuroimaging Award (New Investigator) awarded by the Alzheimer’s Association, and the 2007 recipient of Annals of Neurology’s “Best paper” award for her work on the association of CSF Aβ42 levels with in vivo amyloid imaging.
Dr. Fagan’s lab directs the collection, processing and biomarker analyses of CSF and plasma samples for the KADRC-related projects, as well as several other studies at Wash U and outside academic institutions. The aims of their research are to evaluate the utility of core pathology-associated and novel fluid biomarker analytes for disease diagnosis (who harbors underlying disease pathology) and prognosis (when and how fast will they develop dementia symptoms and how fast will symptoms progress). The Fagan lab also participates in world-wide, collaborative efforts to promote biomarker standardization and validation, criteria that must be met before AD biomarkers are suitable for use in clinical practice.
Updated February 2014