Confirmation of animal models to clarify mechanism of dementia and to develop anti-dementia drugs

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1. Fractal dimension (FD) of senile plaques (SP) of various animal species were calculated and compared. FDs between diffuse (DP) and mature (MP) plaques were significantly different in the dog, monkey and human. In the dog. The FD value and size of SP were plotted. Significant difference was shown between the slope values of the lines of DP and MP. DP and MP were differently formed in these animals. The FD of feline DP was less than those of the dog, monkey, bear, camel and human, indicating special characteristics of feline SP.2. SPs of aged dogs were three-dimensionally (3D) observed. An assembly of amyloid beta (A β) protein of DP was uneven nebula-like structure and that of MP was membrane-like or filamentous one. There were areas of low-density A β deposition inside DP and MP. 3D distribution of amyloid precursor protein, ubiqiutin, glial fibrillary acidic protein and neurofilament were also examined, The results indicated that the two types of SP are formed separately.3. 3D pattern and fractal dimension of assemblies of the two A/β subspecies, I.e. A/β40 and A β42, were investigated. The processes of the 2 types of A β were clarified to be different.4. The distribution of presenilin 1 (PS1) protein in the brain of the eynomoIgus monkey was examined. Carboxyl terminal of PS1 was detected in the cortical neuropil and the deposition was increased with age. The results of the present studies revealed the brain lesions of aged animals. Further, important paradigms in the field of comparative biology such as "SPs are formed but neurofibrilliary tangles are not formed in the nonhuman animals" have been clarified.