Beta amyloid peptide and phosphorylated tau protein expression in the frontal cortex and cerebellum of the toothed whales: preliminary observations and future directions

Abstract

Cetaceans are homeotherms, long-lived top predators, which are at high risk from bioaccumulation and biomagnification of a variety of organic and metallic pollutants. Neurodegenerative diseases, such as Alzheimer’s disease (AD), should be investigated in these animals and considered as a possible cause of stranding. In the present study, we show the preliminary results on the beta amyloid (Aβ) peptide and phosphorylated tau protein expression, the pathological hallmarks of AD, in different species of toothed whales. Beta-amyloid is a 40–43 amino acid peptide cleaved from amyloid precursor protein, and a putative gamma-secretase. It is a major component of the extracellular plaques found in AD brain tissue. Neurofibrillary tangles (NFT) are made up of paired helical filaments, which are insoluble structures composed of a highly phosphorylated form of the microtubule-associated protein tau, and associated lipids. In this study, cerebral and cerebellar were obtained from 9 specimens of 6 different species of the suborder Odontoceti, stranded in the Canary Islands between 2001-2017: the Cuvier’s beaked whale (Ziphius cavirostris), the Blainville’s beaked whale (Mesoplodon densirostris) (n=2), the short-finned pilot whale (Globicephala macrorhynchus), the Risso’s dolphin (Grampus griseus), the bottlenose dolphin (Tursiops truncatus), and the Atlantic spotted dolphin (Stenella frontalis) (n=3). Animals were classiefied as adults (n=6), adult-old (n=1), subadult (n=1), and calf (n=1). Sections were stained with thionine and congo red, the most popular dye used as a probe for diagnosing amyloidosis also in AD brains. The immunoperoxidase staining procedure was carried out on free-floating sections. The antibodies used were a monoclonal anti-beta amyloid antibody and a policlonal anti-NFT antibody. In 5 out of the 9 animals immunopositivity to one of the two antibodies was observed, showing typical and atypical hallmarks of neurodegenerative disease and raising more questions on these animals.