Elizabeth is a fourth year PhD candidate at the University of California, Irvine School of Medicine in the Department of Pathology & Laboratory Medicine. Her work focuses on uncovering sex differences in Alzheimer’s disease through the lens of neuropathology, with a specific emphasis on people with Down syndrome. In addition to characterizing key proteins related to Alzheimer’s disease, she also examines the role of estrogen and its receptors in these pathways and how they may influence the presence of neuropathology. Seeking collaboration across disciplines, Elizabeth served as the Programs Chair for the Sex & Gender Differences Professional Interest Area through the Alzheimer’s Association and helps to organize their annual Great Debate. She was also recently selected as a UC President’s Pre-Professoriate Fellow, as part of the UC-Hispanic Serving Institutions Doctoral Diversity Initiative. Elizabeth is highly passionate about engaging the community outside of academia and participates in Buddy Walks with the Down Syndrome Association of Orange County. In addition, she helps to organize the annual Down Syndrome Showcase at UC Irvine, which highlights the performance and visual arts talents of the local community of people with Down syndrome. In her free time, she enjoys volunteering at the Shea Center for Equine Therapy, spending time with her dog, and practicing martial arts.
Abstract: Estrogen Receptor α Expression is Associated with Alzheimer’s Disease Pathology in People with Down Syndrome
Authors: Elizabeth J. Andrews [1], Freddy Gonzalez [1], Phong T. Ngo [1], Jordan Harp [2], Frederick Schmitt [2], Florence Lai [3], Elizabeth Head [1] and the ABC-DS Consortium.
[1] Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA
[2] Department of Neurology, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY
[3] Department of Neurology Massachusetts General Hospital, Harvard Medical School, Boston, MA
Down syndrome (DS) is associated with early Alzheimer disease (AD). Women with DS show earlier age at menopause and lower bioavailable estrogen. We hypothesized women would have a higher degree of AD pathology at autopsy that would be associated with reduced estrogen receptor alpha (ERα) signaling. Immunohistochemistry for phosphorylated tau (p-tau; AT8), amyloid-β (Aβ; 6E10) and ERα, was performed using brain tissue from 156 individuals (frontal/occipital regions). Groups: DS (n=14/13, 1-39yr), DS with AD (DSAD) neuropathology (n=18/19, 42-61yr), late-onset AD (n=15/16, 72-96yr) and age-matched controls (n=50/47, 2-92yr). Western blotting of cytoplasmic and nuclear sub-cellular fractions was performed using frozen postmortem tissue (DSAD, 7M/7F). An association between Aβ and ERα (p<0.001) and a trend in association with p-tau (p=0.055) in the occipital cortex was observed in women with DS but not in men. Men with DSAD showed elevation in ERα protein in the nuclear and cytoplasmic fractions (p<0.05) compared to women with DSAD in both the occipital and frontal cortex. Women with DSAD may be losing neuroprotective signaling due to estrogen post-menopause, which could accelerate progression of AD pathology. It is critical to understand these differences for clinical trials and to investigate the potential benefit of hormone replacement therapy. Funding Acknowledgement: T32 AG000096, NIH/NIA U19AG068054, P50 AG16573, P30AG066519, BFF170008