Amyloid precursor protein reduction enhances the formation of neurofibrillary tangles in a mutant tau transgenic mouse model.
Neurobiol Aging
; 55: 202-212, 2017 07.
Article
de En
| MEDLINE
| ID: mdl-28464981
ABSTRACT
Alzheimer's disease is characterized by the presence of 2 neuropathological lesions neurofibrillary tangles, composed of tau proteins which are highly phosphorylated and phosphorylated on uncommon sites, and amyloid plaques, containing the Aß peptides generated from the amyloid precursor protein (APP). Reduction of some APP proteolytic derivatives in Alzheimer's disease such as sAPPα fragment has been reported and sAPPα has been shown to affect tau phosphorylation. To investigate in vivo the effect of absence of APP protein and its fragments on tau phosphorylation and the formation of neurofibrillary tangles, we have generated mice deleted for APP gene and overexpressing a human mutant tau protein and developing neurofibrillary tangles (APPKOTg30 mice). These APPKOTg30 mice showed more severe motor and cognitive deficits, increased tau phosphorylation, increased load of neurofibrillary tangles, and increased p25/35 ratio in the brain, compared with Tg30 mice. These data suggest that APP and/or its proteolytic derivatives interfere with the formation of neurofibrillary tangles in a transgenic mouse model that will be useful for investigating the relationship between APP and tau.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Enchevêtrements neurofibrillaires
/
Précurseur de la protéine bêta-amyloïde
/
Protéines tau
/
Maladie d'Alzheimer
/
Mutation
Type d'étude:
Etiology_studies
Limites:
Animals
Langue:
En
Journal:
Neurobiol Aging
Année:
2017
Type de document:
Article
Pays d'affiliation:
Belgique