Pathology

Aged Dogs Exhibit Both Early Amyloid-Aβ and Tau Pathologies
  • Canine amyloid-Aβ (Aβ) protein is identical to the human protein and the pattern and quantity of isoforms is analogous to that seen in humans.
  • Endogenous Aβ is naturally deposited into plaques of the diffuse subtype in aged dogs, which are vulnerable to post translational modification and are fibrillar at the ultrastructural level - cerebral amyloid angiopathy is also found in aged dogs. The pattern of Aβ deposition parallels that seen in humans and occurs over a 3 to 4 year window permitting the examination of interventions that may slow or halt deposition.
  • Cognitive deficits are positively correlated with Aβ deposition in Beagles. Oligomeric forms of Aβ, may correlate with cognitive decline occurring prior to Aβ deposition.
Additional Correlates of AD
  • CSF Aβ42 decreases in the oldest and most impaired Beagles consistent with that seen in conversion to AD
  • Total Tau and Phospho-tau Increases with Age in the Dog
  • Increases in oxidative stress;
  • Neuronal loss and reduced neurogenesis;
  • Reduced MRS markers (e.g., N-acetyl aspartate) of neuronal health;
  • Cholinergic deficits; and
  • Cortical atrophy.