Neurofibrillary Tangles and the Deposition of a Beta Amyloid Peptide with a Novel N-Terminal Epitope in the Brains of Wild Tsushima Leopard Cats

Beta amyloid (Ab) deposits are seen in aged individuals in many of the mammalian species that possess the same Ab amino acid sequence as humans. Conversely, neurofibrillary tangles (NFT), the other hallmark lesion of Alzheimer’s disease (AD), are extremely rare in these animals. We detected Ab deposits in the brains of Tsushima leopard cats (Prionailurus bengalensis euptilurus) that live exclusively on Tsushima Island, Japan. Ab42 was deposited in a granular pattern in the neuropil of the pyramidal cell layer, but did not form argyrophilic senile plaques. These Ab deposits were not immunolabeled with antibodies to the N-terminal of human Ab. Sequence analysis of the amyloid precursor protein revealed an amino acid substitution at the 7th residue of the Ab peptide. In a comparison with other mammalian animals that do develop argyrophilic senile plaques, we concluded that the alternative Ab amino acid sequence displayed by leopard cats is likely to be related to its distinctive deposition pattern. Interestingly, most of the animals with these Ab deposits also developed NFTs. The distributions of hyperphosphorylated tau-positive cells and the two major isoforms of aggregated tau proteins were quite similar to those seen in Alzheimer’s disease. In addition, the unphosphorylated form of GSK-3b colocalized with hyperphosphorylated tau within the affected neurons. In conclusion, this animal species develops AD-type NFTs withou