The primary research interests/findings of Anne Fagan, PhD, 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, the Fagan laboratory collaborateswith domestic and international high-level AD research and clinical labs to formally investigate the within-and between-lab sources of assayvariability.