Alzheimer's disease pathology in the neocortex and hippocampus of the western lowland gorilla (Gorilla gorilla gorilla)

ABSTRACT The two major histopathologic hallmarks of Alzheimer's disease (AD) are amyloid beta protein (Aβ) plaques and neurofibrillary tangles (NFT). Aβ pathology is a common feature in the aged nonhuman primate brain, whereas NFT are found almost exclusively in humans. Few studies have examined AD‐related pathology in great apes, which are the closest phylogenetic relatives of humans. In the present study, we examined Aβ and tau‐like lesions in the neocortex and hippocampus of aged male and female western lowland gorillas using immunohistochemistry and histochemistry. Analysis revealed an age‐related increase in Aβ‐immunoreactive plaques and vasculature in the gorilla brain. Aβ plaques were more abundant in the neocortex and hippocampus of females, whereas Aβ‐positive blood vessels were more widespread in male gorillas. Plaques were also Aβ40‐, Aβ42‐, and Aβ oligomer‐immunoreactive, but only weakly thioflavine S‐ or 6‐CN‐PiB‐positive in both sexes, indicative of the less fibrillar (diffuse) nature of Aβ plaques in gorillas. Although phosphorylated neurofilament immunostaining revealed a few dystrophic neurites and neurons, choline acetyltransferase‐immunoreactive fibers were not dystrophic. Neurons stained for the tau marker Alz50 were found in the neocortex and hippocampus of gorillas at all ages. Occasional Alz50‐, MC1‐, and AT8‐immunoreactive astrocyte and oligodendrocyte coiled bodies and neuritic clusters were seen in the neocortex and hippocampus of the oldest gorillas. This study demonstrates the spontaneous presence of both Aβ plaques and tau‐like lesions in the neocortex and hippocampus in old male and female western lowland gorillas, placing this species at relevance in the context of AD research. J. Comp. Neurol. 521:4318–4338, 2013. © 2013 Wiley Periodicals, Inc. This study used immunohistochemistry and histochemistry to demonstrate the spontaneous appearance of (A) amyloid beta (Aβ) and (B) tau‐like Alzheimer's disease lesions in the neocortex and hippocampus of aged male and female western lowland gorillas. These findings place this species at relevance in the context of AD research.