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
Dr. Anne Fagan, PhD, the Fluid Biomarker Core Leader of the Knight Alzheimer Disease Research Center (ADRC), is a Professor of Neurology at Washington University School of Medicine in St. Louis. She has been involved in fluid biomarker research since 1997 at which time she and her colleagues Drs. David Holtzman and John Morris initiated visionary, longitudinal studies investigating the potential of a variety of fluid measures as biomarkers of preclinical (prior to dementia symptoms) AD pathology in elderly and at-risk middle-aged individuals. Evaluation of fluid biomarkers in individuals with autosomal dominant AD (ADAD) gene mutations (Dominantly Inherited Alzheimer Network, DIAN) and its associated DIAN Trials Unit (DIAN TU) soon followed, as well as expansion evaluating fluid biomarkers in AD due to Down syndrome (Alzheimer Biomarker Consortium – Down Syndrome [ABC-DS]) and early-onset AD (Longitudinal Early-Onset Alzheimer’s Disease Study, [LEADS]).
Dr. Fagan’s primary research interests/findings include:
- Biomarkers in CSF (and more recently, plasma) are useful for identifying underlying AD pathology defined by amyloid and tau positron emission tomography (PET) and brain volumetric measures defined by magnetic resonance imaging (MRI). These data validate the use of CSF (and potentially plasma) markers for disease diagnosis, staging, prognosis and eventual therapeutic efficacy.
- CSF biomarkers are useful for staging individuals during the preclinical/asymptomatic period. The concept of AD as a long, progressive disease that begins several decades prior to clinical symptoms was facilitated by the development of fluid and imaging biomarkers, prompting the proposal of defined diagnostic criteria to include biomarker results. Biomarker profiles observed in LOAD, ADAD and AD due to Down syndrome were instrumental in the crafting/validation of these proposed stages. Such findings are now informing the design and evaluation of prevention trials in AD.
- CSF biomarkers are useful for predicting future cognitive decline in early and pre-symptomatic stages. The critical element required for establishing biomarker validity and utility in early disease stages is its ability to predict future dementia. CSF biomarkers have been shown to predict which cognitively normal individuals will develop cognitive abnormalities within a few years. This information is important clinical trial design for shortening trial duration and reducing cost.
- Despite the utility of established CSF analytes for identifying core AD pathologies and predicting cognitive decline, there still remains a need for markers of additional pathogenic processes (e.g., neuroinflammation and synaptic/neuronal stress and dysfunction). We have reported on several novel markers of neuronal injury and neuroinflammation (e.g., VILIP-1, Ng, YKL-40, SNAP-25) whose levels differ among clinical groups and, when combined with markers of amyloid, predict future cognitive decline.
- Bringing validated biomarkers to clinical practice requires global biomarker standardization efforts. Although CSF biomarkers exhibit excellent diagnostic and prognostic utility when used in research settings, their potential use for individual patient care is limited by inconsistent protocols for sample collection and processing and unacceptable variability in current assay performance. To address these inadequacies, my laboratory has collaborated with domestic and international high-level AD research and clinical labs to formally investigate the within- and between-lab sources of assay variability.
Dr. Fagan is the 2019 recipient of the Fellows Award from the Academy of Science – St. Louis in recognition of her “outstanding achievement in science.” A complete list of Dr. Fagan’s published work can be found in her National Library of Medicine My Bibliography page.
Updated February 2022