Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration.
Neuron
; 51(1): 29-42, 2006 Jul 06.
Article
en En
| MEDLINE
| ID: mdl-16815330
ABSTRACT
Degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive dysfunction in Alzheimer's disease (AD) and Down's syndrome (DS). We used Ts65Dn and Ts1Cje mouse models of DS to show that the increased dose of the amyloid precursor protein gene, App, acts to markedly decrease NGF retrograde transport and cause degeneration of BFCNs. NGF transport was also decreased in mice expressing wild-type human APP or a familial AD-linked mutant APP; while significant, the decreases were less marked and there was no evident degeneration of BFCNs. Because of evidence suggesting that the NGF transport defect was intra-axonal, we explored within cholinergic axons the status of early endosomes (EEs). NGF-containing EEs were enlarged in Ts65Dn mice and their App content was increased. Our study thus provides evidence for a pathogenic mechanism for DS in which increased expression of App, in the context of trisomy, causes abnormal transport of NGF and cholinergic neurodegeneration.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fibras Colinérgicas
/
Precursor de Proteína beta-Amiloide
/
Síndrome de Down
/
Factor de Crecimiento Nervioso
/
Enfermedad de Alzheimer
/
Degeneración Nerviosa
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos