Amyloid-beta E22Delta variant induces synaptic alteration in mouse hippocampal slices.
Neuroreport
; 19(6): 615-9, 2008 Apr 16.
Article
en En
| MEDLINE
| ID: mdl-18382273
ABSTRACT
We recently identified a novel amyloid precursor protein mutation (E693Delta) in familial Alzheimer's-type dementia. This mutation produces amyloid-beta (Abeta) variant lacking glutamate-22 (E22Delta), which showed enhanced oligomerization but no fibrillization. Here, we examined in-vitro toxicity of Abeta E22Delta peptide. Wild-type Abeta1-42 showed a dose-dependent (1 nM to 1 microM) cytotoxicity to cultured neuronal cells in the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assay, whereas Abeta1-42 E22Delta was toxic only weakly at 1 microM. In mouse hippocampal slices, however, Abeta1-42 E22Delta caused a dose-dependent (0.1-10 microM) decrease of synaptophysin, whereas wild-type Abeta1-42 was trophic at 0.1-1 microM and toxic at 10 microM. These results suggest that extracellular Abeta E22Delta causes more potent synaptic alteration, but lower neurodegeneration, than wild-type Abeta probably because of its unique aggregation property.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sinapsis
/
Péptidos beta-Amiloides
/
Hipocampo
/
Neuronas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Neuroreport
Asunto de la revista:
NEUROLOGIA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Japón