Alzheimer's disease (AD) is defined by a clinical state of dementia associated with particular lesions in the brain, neo-cortical "senile" plaques of the neuritic type or of the diffuse type, both of which label with the amyloid βprotein (Aβ) antibody, and neurofibrillary tangle lesions, which are stained with the tau protein and ubiquitin antibodies. Some brains have plaques, some have tangles, and some have both plaques and tangles, suggesting that clinical AD is not an entirely unitary process histopathologically. In advanced disease brain atrophy is prominent. The disease is typically associated with the last trimester or quarter of life. AD has been considered mostly a human disease, since there are no well defined animal models of spontaneous disease, and experimental models are not very satisfactory, in part due to lack of comparability / complexity of brains, and the age issue. A good model will develop the disease spontaneously, and will have similar lesions in similar locations in a complex brain in an aging animal.
Our multi-year investigation of stranded dolphins involves detailed necropsy examination supported by histopathologic study to determine the causes of stranding. Here we report the occurrence of β-amyloid plaques, and their frequency and distribution in the brains of two odontocete species, with special emphasis on the Atlantic bottlenose dolphin, Tursiops truncatus. We have observed plaque lesions in the brain of some animals using ordinary stains, such as hematoxylin and eosin (H&E) and HPS. Use of several commercial antibodies against Aβ and amyloid-specific staining procedures has convincingly demonstrated the presence and composition of plaque lesions.
Forty-eight bottlenose dolphins were included in this study: 9 immature males, 16 mature males, 10 immature females, and 13 mature females. The youngest was newborn, the oldest 38 years. Body length was determined for all 48, body weight for 39 and brain weight for 41. For some (n = 33) ages were determined either by assessment of tooth eruption or by counting dentinal growth layer groups (GLG) in the teeth. It has been reported elsewhere that total body length is not a reliable indicator of age for mature animals, so that animals without age determined by GLG or by tooth eruption, were assigned to an age class by state of gonadal maturity, taking age 10 as the upper limit of a class designated 'immature'. For purposes of analysis, all animals were sorted into three age classes, based on tooth age, tooth eruption, and gonadal activity. These classes are 0-10 years, which included animals aged by GLG, eruption and gonadal status; 11-20 years, based on GLG or gonadal maturity, and 21 + years, based on tooth age alone.
Of the total group of 48 animals, 6, or 12.5% were found to have amyloid-positive plaques. The age class distribution of plaques was age 1-10, 0/19 animals, age class 11-20, 2/18 animals, or 11%, and for age class 21 years and older, 4/11 animals, or 36%. One positive animal in the middle age class was 19 years (GLG); the exact age of the other positive animal in this class was not determined. Brains with plaques could not be distinguished from those without plaques on the basis of weight (absolute), or by calculated brain weight/body length index; i.e., plaques were not associated with detectable brain atrophy.
These findings need to be interpreted in the context of behavioral studies of old animals. However, they suggest that investigation of the brain may offer insights into otherwise unexplainable mass strandings, and to individuals wandering far out of habitat. This study reports for the first time the presence of Alzheimer's like brain alterations in an animal of sea habitat. Striking similarities in age distribution, and in the biochemical/morphological-staining characteristic of the lesions suggest that dolphins might be an excellent model to study the pathogenesis of Alzheimer's disease.