title: Time sequence of maturation of dystrophic neurites associated with Abeta deposits in APP/PS1 transgenic mice.
abstract: Several novel transgenic mouse models expressing different mutant APPs in combination with mutant PS1 have been developed. These models have been analyzed to investigate the formation and progressive alterations of dystrophic neurites (DNs) in relation to Abeta deposits. In the most aggressive model, Abeta deposits appear as early as 2.5 months of age. Maturation of DNs was qualitatively quite similar among models and in some respect reminiscent of human AD pathology. From the onset of deposition, most if not all Abeta deposits were decorated with a high number of APP-, ubiquitin-, and MnSOD-immunoreactive DNs. Phosphorylated Tau DNs, however, appeared at a much slower rate and were more restricted. Mitochondrial dysfunction markers were observed in DNs: the frequency and the density per deposit of DNs accumulating cytochrome c, cytochrome oxidase 1, and Bax progressively increased with age. Later, the burden of reactive DNs was reduced around large compact/mature deposits. In addition, the previously described phenomenon of early intraneuronal Abeta accumulation in our models was associated with altered expression of APP protein as well as oxidative and mitochondrial stress markers occasionally in individual neurons. The present study demonstrates that oxidative and mitochondrial stress factors are present at several phases of Abeta pathology progression, confirming the neuronal dysfunction in APP transgenic mice.
authors.affiliation: Neurodegenerative Disease Group, Centre de Recherche de Paris, Aventis Pharma 94403, Vitry sur Seine Cedex, France. veronique.blanchard@aventis.com
authors.forename: Véronique
authors.initials: V
authors.lastname: Blanchard
authors.forename: Saliha
authors.initials: S
authors.lastname: Moussaoui
authors.forename: Christian
authors.initials: C
authors.lastname: Czech
authors.forename: Nathalie
authors.initials: N
authors.lastname: Touchet
authors.forename: Bruno
authors.initials: B
authors.lastname: Bonici
authors.forename: Michel
authors.initials: M
authors.lastname: Planche
authors.forename: Thierry
authors.initials: T
authors.lastname: Canton
authors.forename: Iness
authors.initials: I
authors.lastname: Jedidi
authors.forename: Micheline
authors.initials: M
authors.lastname: Gohin
authors.forename: Oliver
authors.initials: O
authors.lastname: Wirths
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
authors.forename: Dominique
authors.initials: D
authors.lastname: Langui
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: Günter
authors.initials: G
authors.lastname: Tremp
authors.forename: Laurent
authors.initials: L
authors.lastname: Pradier
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D008163:Luminescent Measurements; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D016501:Neurites / Q000473:pathology*; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology*; D010957:Plasmids / Q000235:genetics; D053764:Presenilin-1; D013312:Stress, Physiological / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D013482:Superoxide Dismutase