- 210 450-8657
DepartmentPharmacology - Biggs Institute for Alzheimer’s and Neurodegenerative Disease
Sarah C. Hopp, Ph.D.
My research focuses on microglia, the immune cells of the central nervous system, and how these cells are involved in Alzheimer’s disease and other age-associated neurodegenerative diseases. Microglia changes during aging, in Alzheimer’s disease and chronic neuroinflammation. A main research objective is to understand how these changes contribute to the initiation and progression of neurodegeneration and cognitive deficits.
One line of my research focuses on microglia interaction with tau pathology. Misfolded tau accumulates and spreads during Alzheimer’s disease and other tauopathies, and recent evidence from my laboratory suggests that microglia contribute to the spread of tau pathology via dysfunctional degradation of tau. Microglia are found near tau tangle-bearing neurons in Alzheimer’s disease brains. It has long been assumed that microglia associate with these pathological aggregates to facilitate clearance of these deposits, although since the lesions persist there is clearly a failure in this process. I have found that microglia from tangle-bearing mouse and human brains contain tau aggregates and these aggregates are capable of inducing tau misfolding in recipient cells. Furthermore, microglia can engulf tau but only partially reduce its ability to transmit aggregates. Overall my work demonstrates a dual role for microglia in tau pathology: one of beneficial clearance and another of contribution to pathology.
A second line of my research focuses on how microglia intracellular calcium dysregulation in the context of Alzheimer’s pathology alters normal microglia processes and contributes to their dysfunction in Alzheimer’s disease. My previous work demonstrated that calcium channel blocking drugs not only reverse memory deficits during chronic neuroinflammation, an early event in Alzheimer’s disease, but that calcium channel blocking drugs are also anti-inflammatory in vivo. A particular interest of my lab is differentiating cell autonomous and non-cell autonomous effects of manipulating calcium channels and microglia in animal models of Alzheimer’s disease and aging.
A variety of methods are utilized to address these research goals including transgenic animal models, behavior analyses, cell culture, imaging, protein biochemistry, flow cytometry, immunohistochemistry and pharmacological and genetic manipulation of microglia-specific pathways.
SB: Brain and Cognitive Sciences; Massachusetts Institute of Technology
PhD: Neuroscience; Ohio State University
Postdoctoral Research: Neurology; Massachusetts General Hospital, Harvard Medical School
|• Microglia||• Alzheimer’s disease|
|• Pharmacology||• Behavioral neuroscience|
|• Aging||• Neuroinflammation|
Sabrina Smith, Lab Manager
Partial reduction of microglia does not affect tau pathology in aged mice. Bennett RE, Bryant A, Hu M, Robbins AB, Hopp SC, Hyman BT. Journal of neuroinflammation. 2018; 15(1):311.
The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer’s disease. Hopp SC, Lin Y, Oakley D, Roe AD, DeVos SL, Hanlon D, Hyman BT. Journal of neuroinflammation. 2018; 15(1):269.
Neuronal calcineurin transcriptional targets parallel changes observed in Alzheimer disease brain. Hopp SC, Bihlmeyer NA, Corradi JP, Vanderburg C, Cacace AM, Das S, Clark TW, Betensky RA, Hyman BT, Hudry E. Journal of neurochemistry. 2018; 147(1):24-39.
Calcium dysregulation via L-type voltage-dependent calcium channels and ryanodine receptors underlies memory deficits and synaptic dysfunction during chronic neuroinflammation. Hopp SC, D’Angelo HM, Royer SE, Kaercher RM, Crockett AM, Adzovic L, Wenk GL. Journal of neuroinflammation. 2015; 12:56.
Differential neuroprotective and anti-inflammatory effects of L-type voltage dependent calcium channel and ryanodine receptor antagonists in the substantia nigra and locus coeruleus. Hopp SC, Royer SE, D’Angelo HM, Kaercher RM, Fisher DA, Wenk GL. Journal of neuroimmune pharmacology. 2015; 10(1):35-44.
Differential rescue of spatial memory deficits in aged rats by L-type voltage-dependent calcium channel and ryanodine receptor antagonism. Hopp SC, D’Angelo HM, Royer SE, Kaercher RM, Adzovic L, Wenk GL. Neuroscience. 2014; 280:10-8.
Age-associated alterations in the time-dependent profile of pro- and anti-inflammatory proteins within the hippocampus in response to acute exposure to interleukin-1β. Hopp SC, Royer S, Brothers HM, Kaercher RM, D’Angelo H, Bardou I, Wenk GL. Journal of neuroimmunology. 2014; 267(1-2):86-91.