title: Intraneuronal APP/A beta trafficking and plaque formation in beta-amyloid precursor protein and presenilin-1 transgenic mice.
abstract: Neuropil deposition of beta-amyloid peptides A beta40 and A beta42 is believed to be the key event in the neurodegenerative processes of Alzheimer's disease (AD). Since A beta seems to carry a transport signal that is required for axonal sorting of its precursor beta-amyloid precursor protein (APP), we studied the intraneuronal staining profile of A beta peptides in a transgenic mouse model expressing human mutant APP751 (KM670/671NL and V7171) and human mutant presenilin-1 (PS-1 M146L) in neurons. Using surface plasmon resonance we analyzed the A beta antibodies and defined their binding profile to APP, A beta40 and A beta42. Immunohistochemical staining revealed that intraneuronal A beta40 and A beta42 staining preceded plaque deposition, which started at 3 months of age. A beta was observed in the somatodendritic and axonal compartments of many neurons. Interestingly, the striatum, which lacks transgenic APP expression harbored many plaques at 10 months of age. This is most likely due to an APP/A beta transport problem and may be a model region to study APP/A beta trafficking as an early pathological event.
authors.affiliation: Department of Psychiatry, University of Bonn Medical Center, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Wirths
authors.forename: Gerd
authors.initials: G
authors.lastname: Multhaup
authors.forename: Christian
authors.initials: C
authors.lastname: Czech
authors.forename: Nicole
authors.initials: N
authors.lastname: Feldmann
authors.forename: Véronique
authors.initials: V
authors.lastname: Blanchard
authors.forename: Günter
authors.initials: G
authors.lastname: Tremp
authors.forename: Konrad
authors.initials: K
authors.lastname: Beyreuther
authors.forename: Laurent
authors.initials: L
authors.lastname: Pradier
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000032:analysis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology*; D016133:Polymerase Chain Reaction; D053764:Presenilin-1; D021381:Protein Transport; D020349:Surface Plasmon Resonance; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1