Imaging the Abeta-related neurotoxicity of Alzheimer disease.
Arch Neurol
; 64(10): 1467-77, 2007 Oct.
Article
em En
| MEDLINE
| ID: mdl-17923630
ABSTRACT
BACKGROUND:
Neurotoxicity related to the Abeta peptide is thought to be a primary mechanism of dysfunction in Alzheimer disease (AD). Although numerous imaging studies have observed brain dysfunction in AD, whether these imaged defects reflect Abeta-related neurotoxicity remains unknown.OBJECTIVE:
To study Abeta-related neurotoxicity by means of functional imaging maps of the hippocampal formation in human patients and mouse models.DESIGN:
Cross-sectional study comparing humans with AD and control subjects, cross-sectional study of J20 mice, a transgenic mouse model of AD, and a longitudinal study of flurbiprofen administration to transgenic mice.SETTING:
Alzheimer disease research center. Subjects Eleven subjects with probable Alzheimer disease and 11 age-matched controls, plus J20 mice and wild-type littermates.INTERVENTIONS:
In the first study, human subjects and controls underwent magnetic resonance imaging. In the second study, mice underwent imaging at 3, 6, 12, 15, and 21 months of age, for a total of 57 imaging experiments. In the third study, 12 J20 mice underwent imaging repeatedly over time; 6 received flurbiprofen to ameliorate Abeta-related neurotoxicity and 6 received vehicle control. MAIN OUTCOMEMEASURES:
Comparison of hippocampal functional maps.RESULTS:
Among all hippocampal subregions, the entorhinal cortex was the dominant site of dysfunction observed in both human patients and J20 mice. Long-term administration of flurbiprofen rescued entorhinal cortex dysfunction in transgenic mice.CONCLUSION:
Our results establish that the neurotoxicity related to the Abeta peptide can be captured in vivo by functional imaging and suggest hippocampal subregions most vulnerable to its toxic effects.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
/
Síndromes Neurotóxicas
/
Doença de Alzheimer
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Aged80
/
Animals
/
Humans
Idioma:
En
Revista:
Arch Neurol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos