Legacy Research Institute

Transforming medical care through science, technology, and innovation.

Danielle M. Osborne, PhD

Danielle M. Osborne, Ph.D.

Associate Staff Scientist
R.S. Dow Neuroscience
Legacy Research Institute

Phone: 503-413-2474  |  Email: dosborne@downeurobiology.org

CV (updated December 2020)
Peer Reviewed Publications
R.S. Dow Neuroscience Laboratories

Short Bio:

Dr. Osborne earned her Ph.D. in Behavioral Neuroscience from the University at Albany focusing on stress interactions with insulin signaling in the dorsal hippocampus with an additional emphasis on glucose metabolism in the hippocampus. She took a post-doctoral position at Legacy Research Institute to work on sex differences in neuropsychiatric disorders. She has since risen within LRI to become a Staff Scientist, and with intramural support she has developed an independent line of research into using obesity models to better understand the sex differences and etiology of Alzheimer’s Disease.

Publication Highlights:

Obesity prevents S-adenosylmethionine-mediated improvements in age-related peripheral and hippocampal outcomes.
Vander Velden, JW, Osborne DM.
Nutrients. (2021) 13(4), 1201

Intrahippocampal administration of a domain antibody that binds aggregated amyloid-β reverses cognitive deficits produced by diet-induced obesity.
Osborne DM, Fitzgerald DP, O'Leary KE, Anderson BM, Lee CC, Tessier PM, McNay EC. 
Biochim Biophys Acta (2016) Jun;1860(6):1291-8.

The neuroenergetics of stress hormones in the hippocampus and implications for memory
Osborne DM, Pearson-Leary J, McNay EC. 
Front Neurosci (2015) May 6;9:164.

Research Interests:

  • Obesity-mediated susceptibility to Alzheimer’s Disease
  • Hippocampal metabolism
  • Sex differences
  • Stress effects in the hippocampus

Research Focus:

The early events that culminate in Alzheimer’s Disease are poorly understood and difficult to study in a clinically relevant way. Although genetic models are an invaluable resource, 95% of Alzheimer’s cases have no clear genetic cause, making it difficult to identify early biomarkers and treatment inventions; often by the time cognitive deficits are apparent, the disease has progressed for over a decade, such that treatments cannot be effective with such severe atrophy of the brain.

Obesity and Type 2 Diabetes confer a 1.5-1.7 fold increase in risk for Alzheimer’s Disease, respectively. The brain undergoes substantial structural and functional changes with long-term consumption of an obesogenic diet. By studying these changes in susceptible brain regions, like the hippocampus, I hope better understand the early molecular events that lead to Alzheimer’s Disease.

Previously, we examined changes in gene methylation stemming from long-term high-fat and high-sugar consumption. An obesogenic diet resulted in substantial promoter and intragenic methylation changes, and subsequent perturbations in mRNA expression of the Alzheimer’s risk gene BIN1, brain-derived neurotrophic factor, histone deacetylases, and other genes related to cognition. We are following up on these results to dive further into autophagy and mTOR related mechanisms that become dysfunctional in obesity.

Of paramount importance, is the full inclusion of males and females in my research. Prior to menopause, females enjoy enhanced neuroprotection from neurosteroids allopregnanolone and estrogen. With advanced age, the sex differences in neurodegeneration narrow; however, the pathways and mechanisms driving that effect can differ between the sexes. Additionally, inclusion of females in obesity and metabolic drivers of Alzheimer’s research is nearly non-existent. This must be remedied.