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Dr. Elizabeth Head

UCI Professor, Vice Chair for Research; Department of Pathology and Laboratory Medicine. Director, Experimental Pathology Program

Dr. Elizabeth Head

Dr. Head received a Masters in Psychology and a Ph.D. in Neuroscience from the University of
Toronto, Canada. She received postdoctoral training at the Institute for Memory Impairments
and Neurological Disorders (UCI MIND) at the University of California – Irvine. She continues to work at the University of California – Irvine as a Professor and Vice Chair for Research in the Department of Pathology and Laboratory Medicine. Dr. Head has been working with a canine model of human brain aging and Alzheimer Disease to test novel interventions that may be translated to people. Dogs naturally develop cognitive decline beginning in middle age that is associated with increased beta-amyloid pathology,
reduced neurogenesis, neuron loss in the hippocampus and increased brain inflammation. She
has over 25 years of experience working with aging dogs, developed cognitive tests to assess
learning and memory in dogs and has an extensive background in measuring AD
neuropathology both in dogs and in human brain samples. Dr. Head has published over 200
peer reviewed papers, over 30 review papers and book chapters and has been funded by the
NIA for her research.

Aging Beagles as a Model for Alzheimer disease: Promoting healthy brain aging.

Beagles naturally develop age-related progressive cognitive decline. Reward motivated
tasks in laboratory aged beagles show losses in executive function, learning and
memory, with spatial abilities being most affected. Interestingly, not all aged dogs
develop cognitive dysfunction and significant individual variability is observed. Beta-
amyloid (Aβ) plaques, similar to those in human aging and Alzheimer disease (AD), also
accumulate in the canine brain and correlate with cognitive dysfunction. Dogs develop
other age-related brain changes such as cerebrovascular pathology and atrophy. Thus,
dogs are excellent models to test prevention approaches that will benefit the pet dog
population and can also be successfully translated to humans. We have conducted
several treatment studies in aged dogs over the past 30 years involving antioxidant
diets, behavioral enrichment, statins and Aβ immunotherapy with modest benefits.
Thus, we have pivoted to prevention studies involving middle aged dogs over the past 5
years. Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT)
transcription factor increases in AD and is associated with synaptic loss,
neurodegeneration, neuroinflammation, Aβ production, and cognitive decline. CN/NFAT
inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic
use of tacrolimus in transplant patients reduces risk of AD. I will describe results of our
5-year prevention study in middle-aged beagles targeting the CN/NFAT pathway in
combination with behavioral enrichment on noninvasive magnetic resonance imaging,
fluid biomarkers and cognitive outcomes. Prevention of AD associated cognitive decline
and neuropathology may lead to successful aging in both dogs and humans.

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