Abstract
ABSTRACTAlzheimer's disease is a leading healthcare challenge facing our society today. Functional magnetic resonance imaging (fMRI) of the brain has played an important role in our efforts to understand how Alzheimer's disease alters brain function. Using fMRI in animal models of Alzheimer's disease has the potential to provide us with a more comprehensive understanding of the observations made in human clinical fMRI studies. However, using fMRI in animal models of Alzheimer's disease presents some unique challenges. Here, we highlight some of these challenges and discuss potential solutions for researchers interested in performing fMRI in animal models. First, we briefly summarize our current understanding of Alzheimer's disease from a mechanistic standpoint. We then overview the wide array of animal models available for studying this disease and how to choose the most appropriate model to study, depending on which aspects of the condition researchers seek to investigate. Finally, we discuss the contributions of fMRI to our understanding of Alzheimer's disease and the issues to consider when designing fMRI studies for animal models, such as differences in brain activity based on anesthetic choice and ways to interrogate more specific questions in rodents beyond those that can be addressed in humans. The goal of this article is to provide information on the utility of fMRI, and approaches to consider when using fMRI, for studies of Alzheimer's disease in animal models.
Highlights
Despite being discovered over 100 years ago and currently affecting millions of people, Alzheimer’s disease (AD; see Glossary, Box 1) is a neurodegenerative disorder for which we still lack a clear mechanistic understanding and effective treatment options
The ability to reliably translate Functional magnetic resonance imaging (fMRI) findings from the bench to the clinic has been hindered by a muddled AD etiology, the lack of a model that fully recapitulates human AD, and difficulties with performing fMRI in animals
Technological developments, such as optogenetics, chemogenetics and virtual reality setups, have the potential to push the boundaries of what can be achieved from performing fMRI studies in animal models of AD
Summary
Despite being discovered over 100 years ago and currently affecting millions of people, Alzheimer’s disease (AD; see Glossary, Box 1) is a neurodegenerative disorder for which we still lack a clear mechanistic understanding and effective treatment options. One tool that has proven invaluable for investigating AD is functional magnetic resonance imaging (fMRI; Box 1) In this approach, powerful magnetic fields are used to record changes in cerebral blood oxygenation, blood volume and blood flow as a way to measure brain activity while a patient performs tasks or is at rest (Logothetis et al, 2001; Ogawa et al, 1992). In the case of AD, dozens of animal models have been generated and investigated over the years Many of these replicate only a single aspect of the disease, such as amyloid plaque buildup or Tau hyperphosphorylation. Researchers can use these models to investigate the pathological impact from individual components of AD. Increased activation of immune cells, such as microglia, leads to downstream pathology
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