title: Alzheimer-associated APP+1 transgenic mice: frameshift beta-amyloid precursor protein is secreted in cerebrospinal fluid without inducing neuropathology.
abstract: Biomarkers present in the cerebrospinal fluid (CSF) of Alzheimer Disease patients could be instrumental in guiding diagnosis and monitoring of progression of the disease. We have previously reported on the secretion of a frameshifted form of amyloid-beta precursor protein, APP+1, into the CSF of Alzheimer patients and controls. APP+1 is secreted efficiently in controls, but during the progression of Alzheimer Disease, its secretion is reduced and APP+1 accumulates in tangle-bearing neurons. Here we describe the generation of a transgenic mouse line expressing APP+1 in the brain. These mice do not suffer from overt pathology or neurodegeneration, suggesting that APP+1 is not neurotoxic. To measure APP+1 levels in the CSF, we serially sampled CSF from the cisterna magna in the same mouse over a period of months. Indeed, APP+1 is secreted into the CSF of the transgenic mice, and APP+1 levels are stable over 1 year. This mouse model may guide the study of secretion deficits as found in Alzheimer Disease.
authors.affiliation: Netherlands Institute for Brain Research, Graduate School for Neurosciences Amsterdam, Meibergdreef 33, 1105 AZ, Amsterdam, The Netherlands. david@cncr.vu.nl
authors.forename: David F
authors.initials: DF
authors.lastname: Fischer
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
authors.forename: Barbara
authors.initials: B
authors.lastname: Hobo
authors.forename: Fred W
authors.initials: FW
authors.lastname: van Leeuwen
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D000818:Animals; D001798:Blood Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D016368:Frameshift Mutation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics*; D014018:Tissue Distribution
chemical_list: D001798:Blood Proteins; C104581:PABPC4 protein, human; D039102:Poly(A)-Binding Proteins