CHARACTERIZATION OF BETA AMYLOID DEPOSITION PROCESS IN THE BOVINE BRAIN: NEUROPATHOLOGICAL, IMMUNOBIOCHEMICAL AND GENETIC FEATURES

Senile and diffuse beta-amyloid (Aβ) plaques represent a characteristic trait of brain aging in both humans and animals. Regarding the latter, a wide range of species, including non-human primates, the dog, the cat, the bear, the wolverine and the camel have been investigated for the presence of cerebral Aβ deposits. However, studies on the presence of Aβ deposits in the bovine brain are still lacking. Aim of this study was to characterize the hallmarks of neurodegeneration in the bovine brain by determining presence, distribution and deposition pattern of Aβ deposits by immunohistochemistry (IHC) and western blot (WB) techniques. Furthermore, the influence of apolipoprotein E (APOE) gene on Aβ-deposition process was also investigated. Formalin-fixed and frozen samples of four brain regions (cerebral cortex, hippocampus, cerebellum and brainstem) obtained from 102 cows (50 healthy and 52 diseased cases) ranging from fetuses to cattle of 240 months of age were examined. Intracellular or glia-associated Aβ deposits were observed by IHC, but a coexistence of these two patterns was often present, particularly in aged cattle. WB analysis showed the deposition of Aβ fragments Aβ 1-38, 1-40, 1-42 and 3-42 in the cerebral cortex and cerebellum. At both IHC and WB analysis the brainstem always appeared spare of Aβ deposits. The genetic variability of the bovine APOE gene was also characterized, assessing that that codons 112 and 158 of the APOE gene are not polymorphic in cattle, contrary to humans. However, nine polymorphisms of the APOE gene were detected, three of which not yet reported in GenBank. Interestingly, a polymorphism at position 876 related to the presence of an extracellular Aβ deposition pattern at the cerebral cortex level was detected. This study demonstrated the presence of Aβ peptides in the bovine brain at different ages and characterized the phenotype of Aβ distribution and deposition pattern. As this study disclosed similar mechanisms of protein aggregation during brain aging in both man and animals, it is conceivable that the bovine brain represents a valid animal model to understand the pathogenic mechanisms of neurodegeneration.