In elderly adults, probably the most common neurodegenerative disease is Alzheimer’s disease (AD). It’s also the leading explanation for dependency and disability. Besides humans, many other animals have been seen to develop certain facets of AD-like pathology. In a latest European Journal of Neuroscience study, scientists studied the brains of Odontocetes (Toothed whales) to document the presence or absence of neuropathological hallmarks of AD. 

Study: Alzheimer’s disease-like neuropathology in three species of oceanic dolphin. Image Credit: Andrew Sutton / Shutterstock

Background

AD has affected tens of millions of older adults worldwide, and its economic impact within the UK alone has been estimated to be over £20 billion annually. When pathognomonic lesions are present beyond a certain stage, disease progression and neurodegeneration occur. This will end in impaired learning skills, memory, communication, and the power to perform day by day tasks. Alois Alzheimer first described amyloid plaques (APs) and neurofibrillary tangles (NFTs) over 100 years ago. Nevertheless, despite ongoing research, there continues to be no preventive or curative treatment for AD.

The buildup of amyloid-beta peptide (Aβ) forms APs and NFTs. These comprise paired helical filaments of hyperphosphorylated tau protein (p-Tau). Nevertheless, research on the etiology and pathogenesis of AD has been hampered attributable to the dearth of animal models that capture the human phenotype. Recently, a number of studies involving deep-diving beaked whales and bottlenose dolphins suggested that these animals needs to be further studied.

In regards to the Study

For this study, samples from specific regions of the brain from 22 stranded odontocetes belonging to 5 different species were examined. These included the Risso’s dolphin (Grampus griseus), long-finned pilot whale (Globicephala melas), white-beaked dolphin (Lagenorhynchus albirostris), harbor porpoise (Phocoena phocoena), and bottlenose dolphin (Tursiops). Immunohistochemistry/fluorescence was used to detect the presence of known markers of AD-like neuropathology. These hallmarks are gliosis, phospho-tau accumulation, and amyloid-beta plaques.

Harbour porpoise or (Phocoena phocoena). Image Credit: onutancu / Shutterstock

Key Findings

Accumulations of APs and p-Tau were noticed in three individual animals, each belonging to a distinct species. Further, the brain lesion distribution in these animals was much like that observed in humans affected by AD. One animal showed well-developed p-Tau accumulation, neuritic plaques, and neuropil threads but no APs. Within the presence of APs, the gliosis and p-Tau accumulation within the brain of dolphins was much like those observed in pinnipeds.

In humans, APs related to AD might be initially positioned within the basal parts of the frontal, temporal and occipital cortices. Because the disease progresses, this spreads to all cerebrocortical areas. The three odontocetes with APs present had analogous accumulations of Aβ in just about all cerebrocortical grey matter. The APs detected were positioned near blood vessels, diffuse, and didn’t have the overt gliosis related to human AD. The importance of the presence of neurodegenerative lesions in odontocetes needs to be examined in future research.

In all brain samples that were examined, microglia and astrocytes were present. Although this was expected, differences in cell numbers and morphology were observed between animals. The three species mentioned above were deemed to develop AD-like neuropathology spontaneously, owing to the concurrent occurrence of hyperphosphorylated tau pathology and APs within the brain. Future research must evaluate the implications of this pathology for overall health and, ultimately, death. It have to be noted that this might explain live stranding in some odontocete species and support the ‘sick-leader’ theory, which describes how social cohesion results in stranding in healthy conspecifics.

It is crucial to focus on that the earliest detection of NFTs in AD patients was in all cortical structures of the hippocampus. Within the case of cetaceans, the hippocampal formation is low, each in absolute and relative terms. In comparison with humans, the scale of the odontocete hippocampus is just 10%. In the present study, unfortunately, the hippocampal region was unavailable across all animals, as this region will not be sampled and identified while investigating the explanation for death. Consequently, the observed neurofibrillary changes within the odontocete brain samples couldn’t be in comparison with those within the hippocampal region of human AD patients. 

Conclusion and Future Research

Humans are closer morphologically to other non-human primates than odontocetes. Nevertheless, the odontocete model to check AD could possibly be more accurate, as non-human primates don’t show the spontaneous development of AD. The findings documented on this study don’t support the hypothesis that shared traits are higher indicators of age-related disorders.

The presence of APs and neurofibrillary changes in odontocetes is very suggestive of some similarity to AD-like pathology in humans. Future research could attempt to validate these findings by increasing the sample size, sampling the hippocampus, and including mysticetes and captive odontocetes. As well as, a greater understanding of AD’s risk aspects, pathogenesis, and underlying mechanisms could possibly be gained by documenting the similarities and dissimilarities in odontocete and human neuropathology compared with incomplete and transgenic models.