【摘 要】
：
The drug discovery for disease-modifying agents in Alzheimer disease (AD) is facing a failure of clinical trials with drugs based on two driving hypotheses, i.e.the cholinergic and amyloidogenic hypot
【机 构】
：
HealthSciences and Technologies-Interdepartmental Center for Industrial Research (HST-ICJR)Universit
【出 处】
：
2013百奥泰波兰重大疾病临床峰会
论文部分内容阅读
The drug discovery for disease-modifying agents in Alzheimer disease (AD) is facing a failure of clinical trials with drugs based on two driving hypotheses, i.e.the cholinergic and amyloidogenic hypotheses.In this presentation we recapitulate the main aspects of AD pathology, focusing on possible mechanisms for synaptic dysfunction, neurodegeneration and inflammation.We then present the pharmacological and neurobiological profile of a novel compound (CHF5074) showing both anti-inflammatory and gamma-secretase modulatory activities, We present the effect of short and long-term treatments in Tg2576 mice on memory tests (NOR and CFC), amyloid burden, brain oligomeric and plasma A levels, intraneuronal A, dendritic spine density/morphology, neuronal cyclin A positivity, activated microglia, cholinergic and glutamatergic transmission, discussing the possible time-window for effective treatment in an AD transgenic mouse model and also in clinical trials.Finally.the concept of cognitive reserve is introduced as possible target for preventive therapies.
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