Alzheimer's disease (AD) is characterized by a progressive loss of cognition and memory function, and is defined pathologically by the deposition of amyloid peptide and neurofibrillary tangles and by a marked cortical cholinergic depletion. In the sporadic form of AD, multiple mechanisms can lead the formation of tangles and plaques. Aim: The MEMORIES hypothesis driven project gathers together 8 partners from 5 different countries towards the aim of developing, characterising and validating new animal models that have a real potential for becoming a gold standard in the AD field. Background/rationale: AD is a complex neurodegeneration possibly determined by multiple molecular mechanisms. One recent finding demonstrated that it can be linked to an unbalanced signaling and processing of the pro-NGF/NGF and pro-BDNF/BDNF signalling pathways. Moreover, the involvement of SorLA, a member of a novel family of vacuolar protein sorting 10 protein (Vps10p)-domain receptors, in APP processing and trafficking has been recently suggested. On the basis of these molecular mechanisms, new mouse models will be created. Description: towards the MEMORIES aim, a panel of mouse models will be, using a multidisciplinary approach, produced and analyzed for the presence of neurodegeneration. These mice will express specific antibodies neutralizing TrkA receptors or mutated form of pro-NGF. AD11 anti-NGF, which already represent a good model for sporadic AD, will be crossed to mice in which the human APP or Tau are over-expressed or to mice in which pro-convertases or the TrkB or SorLA receptors are knocked-out. Mice will be analyzed using standardized for neuroanatomy and behavioural analysis. Anticipated output: We anticipate that by blocking different signaling pathways will help in ameliorating the current available experimental mouse models, being also useful to develop new therapeutic tools for this disease and strengthen European competitiveness in the war against'.
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Funding SchemeSTREP - Specific Targeted Research Project