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Abstract

Transactive response DNA binding protein of 43 kDa (TDP-43) is a ubiquitously expressed nuclear protein involved in RNA metabolism and stress granule formation. Pathological inclusions and mislocalization of this protein in brain cells is pathognomonic or concurrent across a wide range of neurodegenerative diseases, and has been implicated in age-associated cognitive decline. In these pathologies, TDP-43 becomes mislocalized, forming inclusions in the cytoplasm, nucleus, and cell processes. In these inclusions, TDP-43 undergoes aberrant post-translational modifications, often phosphorylation. This investigation assessed the presence of TDP-43 pathology and mislocalization in the amygdala, entorhinal cortex, and prefrontal cortex of aged rhesus macaques. Endogenous TDP-43 pathology in the macaque brain has not been well described. We hypothesized that the macaque exhibits histological TDP-43 phenotypes resembling those found in human neurodegeneration and cognitive decline.

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