Margaret Flanagan, MD

Assistant Professor, Department of Laboratory Medicine and Pathology

Margaret Flanagan

Contact Info

mflanaga@umn.edu

Office Phone 612-625-6419

Office Address:
WMBB C514-1 (research office)
Phone: 612-625-6419 (research)
C-514-1 Mayo (clinical office)
Phone: 612-624-6563 (clinical)

MD (MB, BCh, BAO), Trinity College Dublin, 2013

Residency in Anatomic Pathology, University of Washington, 2015

Fellowship in Anatomic Pathology / Neuropathology, Stanford University, 2017

Fellowship in Neuropathology, University of Washington, 2016

BS, Cytotechnology, cum laude, University of North Dakota, 2008

Summary

Dr. Flanagan is an anatomic pathologist and neuropathologist whose research focus is on neurodegenerative diseases including Alzheimer’s disease and spinocerebellar ataxia. She is the department’s lead investigator for the Nun Study of Aging and Alzheimer's disease, a longitudinal study launched in 1986 to determine the causes and prevention of Alzheimer’s disease, other brain diseases, and mental and physical disability associated with old age.

Flanagan specializes in analyzing human brain samples at autopsy. She participates in studies of community-based epidemiologic cohorts such as the ACT (Adult Changes in Thought) Study, a collaboration between the University of Washington and Kaiser Permanente (formerly Group Health). The ACT study is a community-based cohort with the requirement that subjects be community dwelling, 65 years of age or older and not demented at time of entry. Investigators track subject changes, exposures, and lifestyles and analyze various samples and genetic factors, with the data endpoint a brain autopsy. The purpose of the ACT study is to prospectively examine the incidence of Alzheimer’s disease and dementia, as well as risk factors for these conditions. Flanagan and her colleagues have found that ACT participants with higher prescription non-steroidal anti-inflammatory drug (NSAID) exposure had increased concentrations of ?-amyloid, the main component of amyloid plaques found in Alzheimer’s disease, and that ACT participants with higher prescription opioid exposure had increased concentrations of phospho-tau, the main component seen in neurofibrillary degeneration in Alzheimer’s disease.

The National Institute on Aging (NIA) and the Alzheimer’s Association (AA) established neuropathologic guidelines in 2012 for diagnosing dementia that include the distribution and density of plaques and distribution of tau protein neurofibrillary tangles. Investigators including Flanagan have developed what they term the “condensed protocol” that meets or exceeds the 2012 NIA-AA guidelines for diagnosing Alzheimer’s Disease, Lewy body dementia, and microvascular lesions while simultaneously reducing time and cost.

Because traditional assessments can be subjective, Flanagan is developing newer technologies that can more objectively quantify these abnormal proteins. She has worked with Histelide, a novel antibody capture assay developed at the University of Washington that can be used to obtain quantitative and localization data, and currently is working with the development of disease-specific panels using multiplex ion-beam imaging (MIBI), which allows neuropathologists to analyze expression levels of thirty or more antibodies on a single slide using mass spectrometry. Flanagan and her colleagues are designing and optimizing MIBI panels for studies of healthy aging, Alzheimer’s disease, Lewy body dementia, and other cognitive disorders. She thinks MIBI and other multiplexing technologies will be especially helpful in both identifying and understanding the multiple disease processes that often coexist in individual dementia patients. Co-existing brain neuropathologies suggest that the interaction of amyloid plaques, tau neurofibrillary tangles, inflammatory factors, genetics, and other entities is fundamental to the development of cognitive decline. Understanding such complex interactions is key to understanding the disease pathobiology and identifying new pathways for treatment and prevention. Large datasets from community-based epidemiological cohorts are required to sort out these complex interactions and to find genetic factors associated with different ethnic groups.

Flanagan is working with a multi-institutional team that is combining the cohorts of the Nun Study, comprising mainly Caucasian Roman Catholic School Sisters of Notre Dame who were born in the U.S. between 1890 and 1916, with the Honolulu-Asia Aging Study (HAAS), comprising men of Japanese ancestry born on Oahu between 1900 and 1919. Flanagan and fellow investigators have evaluated epidemiologic data and observational neuropathologic findings with the aim of identifying similarities between the cohorts that will help clarify both the pathophysiology of Alzheimer’s disease and cognitive resilience in these two very different groups. She will continue to work with multiplexing and objective quantification platforms studying longitudinal cohorts in an attempt to better understand dementia and aging.

Expertise

Anatomic Pathology, Neuropathology

Research

Publications

PubMed

Flanagan ME, Larson EB, Walker RL, Keene CD, Postupna N, Cholerton B, Sonnen J, Dublin S, Crane PK, Montine TJ. Associations between use of specific analgesics and concentrations of amyloid-? 42 or phosphor-tau in regions of human cerebral cortex. Journal of Alzheimer’s Disease. Vol. 61, no.2, pp 653-662, 2018. https://www.ncbi.nlm.nih.gov/pubmed/29226863

Latimer CS, Flanagan ME, Cimino PJ, Jayadev S, Davis M, Hoffer ZS, Montine TJ, Gonzalez-Cuyar LF, Bird TD, Keene CD.  Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.  J Huntingtons Dis. 2017 Oct 11. doi: 10.3233/JHD-170261. [Epub ahead of print]

Turk K, Flanagan ME, Josephson S, Keene CD, Jayadev S. Psychosis in spinocerebellar ataxias: a case series and study of Tyrosine Hydroxylase in substantia nigra. The Cerebellum. 2017 Sept; 1-9. doi: 10.1007s12311-017-0882-5 https://link.springer.com/article/10.1007/s12311-017-0882-5

Bharadwaj R, Cimino PJ, Flanagan ME, Latimer CS, Gonzalez-Cuyar LF, Juric-Sekhar G, Montine TJ, Marshall DA, Keene CD. Application of the Condensed Protocol for the nIA-AA guidelines for the neuropathologic assessment of Alzheimer’s disease in an academic clinical practice. Histopathology 2017 Aug; doi:10.1111/his.13345 http://onlinelibrary.wiley.com/doi/10.1111/his.13345/full

Caitlin S. Latimer, MD, PhD, C. Dirk Keene, MD, PhD, Margaret E. Flanagan, MD, Laura S. Hemmy, PhD, Kelvin O. Lim, MD, Lon R. White, MD, MPH, Kathleen S. Montine, PhD, Thomas J. Montine, MD, PhD.  Resistance to Alzheimer Disease Neuropathologic Changes and Apparent Cognitive Resilience in the Nun and Honolulu-Asia Aging Studies. Journal of Neuropathology & Experimental Neurology, Volume 76, Issue 6, 1 June 2017, Pages 458–466, https://doi.org/10.1093/jnen/nlx030

Margaret E. Flanagan, Desiree A. Marshall, Jane B. Shofer, Kathleen S. Montine, Peter T. Nelson, Thomas J. Montine and C. Dirk Keene.  Performance of a Condensed Protocol That Reduces Effort and Cost of NIA-AA Guidelines for Neuropathologic Assessment of Alzheimer Disease.  J Neuropathol Exp Neurol 76 (1): 39-43) January 2017, doi: 10.1093/jnen/nlw104

Flanagan M, Larson EB, Latimer CS, Cholerton B, Crane PK, Montine KS, White LR, Keene CD, Montine TJ. Clinical-pathologic correlations in vascular cognitive impairment and dementia. Biochimica et Biophysica Acta–Molecular Basis of Disease 2016 May; 1862(5): 945-51. PMID:26319420.

Cholerton B, Larson EB, Quinn JF, Zabetian CP, Mata IF, Keene CD, Flanagan M, Crane PK,Grabowski TJ, Montine KS, Montine TJ. Precision medicine: clarity for the complexity of dementia. American Journal of Pathology 2016 March; 186(3): 500-6. PMID: 26724389

Ene CI, Nerva JD, McGrath L, Flanagan ME, Chamberlain MC, Silbergeld DL. Flow related aneurysm within glioblastoma: A case report and review of the literature. World Neurosurg. 2016. February. pii:S1878-8750(16)00156-X. doi: 10.1016/j.wneu.2016.01.068. [Epub ahead of print].

Zha BS, Flanagan M, Coulson C, Garvin KW, Zaas AK, Marrie TJ. Difficult to Identify: Malignant Peritoneal Mesothelioma. American Journal of Medicine. 2015 November (128) 11:1191-1194. PMID: 26164565

Clinical

Board Certifications

Anatomic Pathology, Neuropathology