title: APP transgenic mice and their application to drug discovery.
abstract: The development of transgenic mice expressing mutated forms of the human amyloid precursor protein (APP) and presenilin-1 (PS1), proteins associated with familial forms of Alzheimer's disease (AD), has provided a backbone for translational studies of potential novel drug therapies. Such mice model some aspects of AD pathology in that they develop senile plaque-like deposits of the amyloid beta-protein (Aβ) together with inflammatory pathology and some degree of neurodegeneration. Aβ deposition is considered to be a potentially pathogenic feature of AD and drug discovery programmes utilising such mice and associated with drugs now reaching the clinic have been largely directed towards decreasing the deposition. This goal has been achieved in the mouse models, although the agents developed have not, to date, shown evidence of efficacy in AD sufferers and, in some cases, have worsened the clinical state. Nevertheless, reducing the pathological features of the disease continues to be the objective of pharmacological intervention and ongoing programmes continue to use transgenic mice expressing mutated APP and PS1 transgenes in attempts to overcome issues and difficulties arising from the initial clinical trials and to explore new approaches to AD treatment.
authors.affiliation: King's College Wolfson Centre for Age Related Diseases, King's College London, St Thomas' Street, London, UK. david.howlett@kcl.ac.uk
authors.forename: D R
authors.initials: DR
authors.lastname: Howlett
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D023582:Alzheimer Vaccines / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D018696:Neuroprotective Agents / Q000494:pharmacology*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C545487:APP protein, human; D023582:Alzheimer Vaccines; D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; C508853:PSEN1 protein, human; D053764:Presenilin-1