Histochemical accumulation of oxidative damage products is associated with Alzheimer-like pathology in the canine

Topic: Brain proteins, microglia and lab models

An important lesion in Alzheimer's disease (AD) patient brains is the neurofibrillary tangle (NFT). Hyperphosphorylated tau is its major component. In a former paper we described some NFT in the canine brain. During aging, moreover, advanced glycation end products (AGE) might accumulate. Glycated tau induces lipid peroxidation in vivo and tau and AGE antigens have been mentioned to co-localize in NFT. This indicates that AGE may play an important role in Alzheimer disease (AD) by oxidation of tau. The aim of the present study was to investigate amyloid, neurofibrillary tangles, Abeta precursor protein, Abeta, tau, ubiquitin, advanced glycation end products, 4-hyroxynonenal protein and lipofuscin in a series of dogs of varying ages. The results showed a significant positive correlation between age and amyloid quantity (Congo red staining), HNE staining and lipofuscin (LF), and between amyloid quantity and HNE staining and LF. Staining for AbetaPP seemed to have a tendency to increase with age, whereas staining for tau, ubiquitin and AGE each only gave limited positive results in a proportion of the older dogs. Preliminary studies including loss of cognitive capabilities in the older dogs and chemical measurement of lipofuscin-like pigment (LFP) accumulation in brain extracts revealed an increase with old age and dementia. The Congo red, HNE and LF results suggest that deposition of amyloid with aging might be associated with formation of end products of lipid peroxidation. The finding of the limited positive signals for tau, ubiquitin and AGE in some old cases might indicate that the spontaneous brain pathology of the aged dog reveals similarities to early stages observed in AD in humans especially those with Down syndrome.

@article{rofina2004-15478464,
  author  = {Rofina, J. E. and Singh, K. and Skoumalova-Vesela, A. and van Ederen, A. M. and van Asten, A. J. and Wilhelm, J. and Gruys, E.},
  title   = {{Histochemical accumulation of oxidative damage products is associated with Alzheimer-like pathology in the canine}},
  journal = {Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis},
  year    = {2004},
  doi     = {10.1080/13506120412331285779},
  pmid    = {15478464},
  url     = {https://doi.org/10.1080/13506120412331285779}
}

Key findings

• This indicates that AGE may play an important role in Alzheimer disease (AD) by oxidation of tau.
• The results showed a significant positive correlation between age and amyloid quantity (Congo red staining), HNE staining and lipofuscin (LF), and between amyloid quantity and HNE staining and LF.
• Staining for AbetaPP seemed to have a tendency to increase with age, whereas staining for tau, ubiquitin and AGE each only gave limited positive results in a proportion of the older dogs.
• Preliminary studies including loss of cognitive capabilities in the older dogs and chemical measurement of lipofuscin-like pigment (LFP) accumulation in brain extracts revealed an increase with old age and dementia.
• The Congo red, HNE and LF results suggest that deposition of amyloid with aging might be associated with formation of end products of lipid peroxidation.

Why it matters

In a series of dogs of varying ages, this study found age-related increases in amyloid, oxidative damage markers and lipofuscin, with preliminary signs of cognitive loss in older dogs. This is animal research and does not show any treatment, cure or prevention for Alzheimer's disease in people.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1080/13506120412331285779
• PubMed: 15478464
• Original source →

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