Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment.
Single and double-labeling immunocytochemistry has been used to learn about the localization, distribution, and possible relationship between beta-amyloid protein (Aβ) deposition and tau hyperphosphorylation in the canine cerebral cortex with age. Behavioral impairment, as reported by the owners and tested in all dogs, correlated with increased Aβ burden in old dogs. Aβ plaques were diffuse and they were not accompanied by modifications in synaptic protein expression. Plaques were not associated with increased active mitogen activated protein kinase (MAPK/ERK-P) and p38 kinase (p38-P) expression, and tau hyperphosphorylation in neighboring cell processes. Yet tau hyperphosphorylation, as revealed with phospho-specific antibodies to tauThr181 and tauSer396, increased with age in individual neurons. Moreover, the subcellular pattern shifted from perinuclear localization to granular cytoplasmic and nuclear distribution with age. Our results in dog suggest that Aβ diffuse plaque formation and tau hyperphosphorylation are independent events, both occurring during the process of aging. Although increased cognitive dysfunction is associated with increased tau hyperphosphorylation, further investigation is needed to understand whether tau hyperphosphorylation is causative of cognitive impairment or an independent process related to aging.