Activated gliosis, accumulation of amyloid β and hyperphosphorylation of tau in aging canines with and without cognitive decline

Abstract

Canine cognitive dysfunction (CCD) syndrome is a well-recognized naturally occurring disease in aged dogs, with a remarkably similar disease course, both in its clinical presentation and neuropathological changes, as humans with Alzheimers disease (AD). Similar to human AD patients this naturally occurring disease is found in the aging canine population however, there is little understanding of how the canine brain ages pathologically. It is well known that in neurodegenerative diseases, there is an increase in inflamed glial cells as well as an accumulation of hyperphosphorylation of tau (P-tau) and amyloid beta (Amyloid beta 1-42). These pathologies increase neurotoxic signaling and eventual neuronal loss. We assessed these brain pathologies in aged canines and found an increase in the number of glial cells, both astrocytes and microglia, and the activation of astrocytes indicative of neuroinflammation. A rise in the aggregated protein Amyloid beta 1-42 and hyperphosphorylated tau, at Threonine 181 and 217, in the cortical brain regions of aging canines is seen. We then asked if any of these aged canines had CCD utilizing the only current diagnostic, owner questionnaires, verifying positive or severe CCD had pathologies of gliosis and accumulation of Amyloid beta1-42 like their aged matched controls. However uniquely the CCD dogs had P-tau at T217. Therefore, this phosphorylation site of tau at threonine 217 may be a predictor for CCD

Postoperative Cognitive Dysfunction and Virtual Reality for Cognitive Rehabilitation in Cardiac Surgery Patients: A Short Review

“…A prospective longitudinal study of older cardiac surgery patients found that the prevalence of dementia 7.5 years after interventions was significantly higher than the population prevalence [12]. Animal studies also indicate that surgery and anesthesia contribute to cognitive decline and AD-associated neuropathologic changes, including neuroinflammation, Aβ aggregation, and tau hyperphosphorylation [30,31].…”

How calcineurin inhibitors affect cognition

“…Dogs also exhibit age-related amyloid plaque pathology, neuroinflammation, and neurodegeneration, making them particularly suitable for studying anti-AD therapy. 72 A study using middle-aged beagles found protective effects of one-year tacrolimus treatment against age-and AD-related brain microstructural changes, as measured by higher-order diffusion magnetic resonance imaging (MRI) metrics. The authors found that long-term and low-dose administration of tacrolimus reduced the neurite density index (NDI), detected inflammation as cellular edema results in increased volume without increased orientation dispersion index (ODI), a diffusion metric positively correlated with microglial density in hippocampal and parahippocampal gyri of experiment animals.…”

“…Canines possess a metabolic system that closely resembles that of humans. Dogs also exhibit age‐related amyloid plaque pathology, neuroinflammation, and neurodegeneration, making them particularly suitable for studying anti‐AD therapy 72 . A study using middle‐aged beagles found protective effects of one‐year tacrolimus treatment against age‐ and AD‐related brain microstructural changes, as measured by higher‐order diffusion magnetic resonance imaging (MRI) metrics.…”