Amyloid-β and phosphorylated tau screening in bottlenose dolphin (Tursiops truncatus) and striped dolphin (Stenella coeruleoalba) brains from Italy reveals distinct immunohistochemical patterns correlating with age and co-morbidity

: Cetacean brains are uniquely adapted to diving, but can be affected by diseases and exposure to toxins, triggering neurodegenerative processes that may cause stranding. Some species exhibit a significant post-reproductive lifespan (PRLS), increasing the likelihood of observing cumulative and age-related pathology. Immunohistochemistry against amyloid-β and hyperphosphorylated tau proteins is increasingly implemented to assess Alzheimer's Disease-like neuropathology in cetaceans, but comparisons between geographically distinct populations, animals of different age groups, sex, and with concomitant pathologies are lacking. We tested 43 cetaceans' (30 Tursiops truncatus; 13 Stenella coeruleoalba) parietal cortex, our most consistently archived cerebral tissue, in immunohistochemical analyses with amyloid-β oligomer 42 (Aβ-42) and hyperphosphorylated tau (pTau AT180 and AT8) antibodies. Aβ-42 antibody cross-reacted with plaques in three aged bottlenose and two aged striped dolphins, but was more often detected within neurons, glia, and blood vessels of all the dolphins. Histoscore comparisons between dolphins of different ages, sexes, and pathologies revealed significant correlations between older age, viral infections, and plaque presence. Protozoan cysts cross-reacted with Aβ-42 antibody. pTau signal was observed as single foci in neurons and neuropil in two young and two aged bottlenose dolphins. To our knowledge, this study is the first of its kind for the Mediterranean region and will help establish baseline understanding of physiological and pathological expression of proteins associated with human neurodegenerative disease in cetacean brains.