The Screening Of Macaque Transgenic Vector Viruses And The Establishment Of A New Macaque Cognitive Automatic Test System

Alzheimer’s disease (AD), characterized with pathological features of senile plaques and neurofibrillary tangles, is a neurodegenerative brain disease. About AD pathology, the two most influential hypotheses are the amyloid cascade hypothesis and tau protein hypothesis. AD starts mostly at old age, and cognitive function of Alzheimer’s patients is progressively lost, memory impairment in it as an early manifestation. After Alzheimer’s patients are diagnosed, the remaining average survival time of them is only about5.7years, and they, who always need someone to take care, can’t take care of themselves in the middle-late stage of AD. Alzheimer’s patients, whose number has more than26million and increase gradually, bring heavy financial and emotional burden on the family and society. AD has no effective treatment so far, and many drugs, developed from mouse models, had disappointing results when they were used in clinical trials. Rhesus monkey has more closely genetic relationship with human, and Aβ plaques were found in the old rhesus monkey brain. Therefore, the develoment of rhesus monkey models, which can reflect AD progression, to explore the disease mechanism of AD and to find effective methods of diagnosis and treatment, in additon to be an urgent problem to be solved, is of great scientific significance.Our laboratory will inject the viruses carrying familial AD genes, or fibrillar Aβ42that is synthesized and cultured in vitro, into the cerebral cortex of rhesus monkey brain, to establish AD monkey model. There are two key preparatory work for modeling. First, need to select suitable virus carriers to prepare for the next transgenic work. Second, need to establish a new cognitive test system to evaluate the experimental manipulations on learning and memory function of the monkeys. These two parts of work constitutes the main content of this paper.In virus screening, according to the literatures,15kinds of viruses were tested. All of them are the lentivirus and adeno-associated viruses.In the monkey brains only AAV2and AAV2/9had expressions, while the control experiment in rat brains, only the lentivirus of carrying the Swedish/Dutch/London AD gene, AAV2/8, AAV2and AAV2/9had expressions and, based on this, we also worked out an appropriate virus injection protocal. In establishing monkey cognitive system, for the first time in China, we have set up a touch screen cognition automated test new system for free moving rhesus monkey. The system has four kinds of test softwares, and is used primarily for testing of spatial and non-spatial working memory in rhesus monkeys. Three monkeys have learnt the visuospatial learning task and all of them have done1000trials in this system. Moreover, we have also developed an effective monkey training procedure. All these works have laid important groundwork for the development of AD monkey models.