Characterization of the Dunkin Hartley guinea pig as a non-transgenic and multimorbid model of brain aging
Date
2024
Journal Title
Journal ISSN
Volume Title
Abstract
Alzheimer's Disease and Alzheimer's Disease Related Dementia (AD/ADRD) affect an estimated 55 million people worldwide; a staggering figure that is expected to grow in the coming years. With this projection looming, we have yet to identify any effective cures, treatments, or preventative strategies. Historically, AD/ADRD research is conducted using genetically engineered pre-clinical models, that express a specific brain aging pathology. Recent discoveries, however, have identified a dynamic whole-body "inflammaging" phenotype that exists with, and likely contributes to, AD/ADRD onset and progression. Currently, we do not have an accessible and tractable preclinical model that naturally mimics the age-related, systemic and progressive neurodegenerative phenotype present in humans. Recent findings, however, suggest the Dunkin Hartley guinea pig (HGP) may address this need. HGPs are known to develop systemic inflammation and progressive age-related comorbidities characteristic of human aging. The presence of this whole-body aging phenotype prompted investigation into the brain. Genetic and transcriptomic analyses found aged HGPs exhibit strong sequence homology, and similar protein expression patterns to human brain aging and AD. Further, immunohistochemical assessment found aged HGPs express markers of neuroinflammation and misfolded proteins in the hippocampus. To further interrogate these novel findings, we examined the histopathology of 4 brain regions often implicated in neurodegenerative decline for evidence of progressive neuropathology. Our results identify the presence of an age related neuroinflammatory and phosphorylated tau phenotype. Findings from this study contribute to the overarching hypothesis that AD/ADRD is a whole-body disease, and ultimately support the goal of closing the existing translational gap between preclinical and clinical neurodegenerative research.
Description
Rights Access
Subject
brain aging
non-transgenic
preclinical
Dunkin Hartley guinea pig
Alzheimer's disease
novel