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.
Recent publications
- Pattern and implications of neurological examination findings in autosomal dominant Alzheimer diseasefor the Dominantly Inherited Alzheimer Network, Feb 2023, In: Alzheimer's and Dementia. 19, 2, p. 632-645 14 p.Research output: Contribution to journal › Article › peer-review
- Multimodal brain age estimates relate to Alzheimer disease biomarkers and cognition in early stages: a cross-sectional observational studyDominantly Inherited Alzheimer Network, 2023, In: eLife. 12, e81869.Research output: Contribution to journal › Article › peer-review
- Cross-sectional and longitudinal comparisons of biomarkers and cognition among asymptomatic middle-aged individuals with a parental history of either autosomal dominant or late-onset Alzheimer's diseaseand Dominantly Inherited Alzheimer Network (DIAN), 2023, (Accepted/In press) In: Alzheimer's and Dementia.Research output: Contribution to journal › Article › peer-review
- Biomarker clustering in autosomal dominant Alzheimer's diseasefor the Dominantly Inherited Alzheimer Network (DIAN), Jan 2023, In: Alzheimer's and Dementia. 19, 1, p. 274-284 11 p.Research output: Contribution to journal › Article › peer-review
- Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer's disease: a cross-sectional studyAlzheimer's Biomarker Consortium-Down Syndrome & Dominantly Inherited Alzheimer Network, Jan 2023, In: The Lancet Neurology. 22, 1, p. 55-65 11 p.Research output: Contribution to journal › Article › peer-review
- Erratum: Comparative Analysis of Alzheimer's Disease Cerebrospinal Fluid Biomarkers Measurement by Multiplex SOMAscan Platform and Immunoassay-Based Approach (Journal of Alzheimer's Disease (2022) 89 (193–207) DOI: 10.3233/JAD-220399)Timsina, J., Gomez-Fonseca, D., Wang, L., Do, A., Western, D., Alvarez, I., Aguilar, M., Pastor, P., Henson, R. L., Herries, E., Xiong, C., Schindler, S., Fagan, A. M., Bateman, R. J., Farlow, M., Morris, J., Perrin, R. J., Moulder, K., Hassenstab, J., Voglein, J., & 4 othersChhatwal, J., Mori, H., Ju Sung, Y. & Cruchaga, C., 2023, In: Journal of Alzheimer's Disease. 91, 2, p. 911 1 p.Research output: Contribution to journal › Comment/debate
- Mendelian randomization and genetic colocalization infer the effects of the multi-tissue proteome on 211 complex disease-related phenotypesYang, C., Fagan, A. M., Perrin, R. J., Rhinn, H., Harari, O. & Cruchaga, C., Dec 2022, In: Genome medicine. 14, 1, 140.Research output: Contribution to journal › Article › peer-review
- AD-causing variants that affect PSEN1 transmembrane domains are associated with faster neurodegeneration and cognitive decline compared to those affecting cytoplasmic domains.Schultz, S. A., Allegri, R. F., Schultz, A. P., Goate, A., Levey, A. I., Fagan, A. M., Hanseeuw, B. J., Koeppe, R. A., Gordon, B. A., Cruchaga, C., Karch, C. M., Chen, C. D., Xiong, C., Jack, C. R., Fitzpatrick, C. D., McDade, E., Chui, H. C., Mori, H., Lee, J. H., Noble, J. M., & 23 othersHassenstab, J. J., Levin, J., Morris, J. C., Johnson, K. A., Liu, L., Farlow, M. R., Jucker, M., Farrell, M. E., Graff-Radford, N. […]
- Racial differences in longitudinal Alzheimer's disease biomarkers among cognitively normal adultsXiong, C., Luo, J., Schindler, S. E., Fagan, A. M., Benzinger, T., Hassenstab, J., Balls-Berry, J. E., Agboola, F., Grant, E., Moulder, K. L. & Morris, J. C., Dec 2022, In: Alzheimer's and Dementia. 18, 12, p. 2570-2581 12 p.Research output: Contribution to journal › Article › peer-review
- Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluidDominantly Inherited Alzheimer Network, Nov 17 2022, In: Nature. 611, 7936, p. 585-593 9 p.Research output: Contribution to journal › Article › peer-review