The main reason Alzheimer's disease (AD) is thought to be a human illness is the lack of reliable animal models for spontaneous disease. The complexity and comparability of the brain, along with age-related problems, present challenges for experimental animal models. Recently, Amyloid-β (Aβ) plaques (APs) and phosphorylated tau (ptau) changes in neurons and neuropil were observed in different mammal species, with very few descriptions in cetaceans. This study describes Aβ deposition in the brain tissue of a female striped dolphin (Stenella coeruleoalba) stranded in the Ligurian coast of the Pelagos Sanctuary. The 18-year-old dolphin, submitted for complete postmortem investigations, presented a moderate pyogranulomatous encephalitis, with diffuse gliosis and multiple nodules of microglia. Five different areas of cerebral and cerebellar cortex underwent immunohistochemical analysis. The immunolocalization of Aβ was tested using mOC64 monoclonal antibody (mAb) while pTau was detected through AT180 and AT8. Brain tissues from AD patient and an Atlantic spotted dolphin (S. frontalis) stranded in the Canary Islands, served as positive control sections. Extracellular and intracellular Aβ deposition, forming APs, was observed in the frontal cortex, while labelling of pTau tested through AT8 mAb, was present in the parietal cortex of the studied animal. No labelling was detected by AT180 mAb. Our initial results support the hypothesis that cetaceans, in particular toothed whales, might spontaneously exhibit AD-like pathology, possibly serving as unique natural models for AD. However, assessing clinical signs essential for an AD diagnosis proves challenging. Work founded by the Italian Ministry of Health (IZSPLV 06/22 RC)