Blocking the apolipoprotein E/amyloid ß interaction in triple transgenic mice ameliorates Alzheimer's disease related amyloid ß and tau pathology.
J Neurochem
; 128(4): 577-91, 2014 Feb.
Article
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| MEDLINE
| ID: mdl-24117759
ABSTRACT
Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late-onset Alzheimer's disease (AD). Studies have shown that the binding between apoE and amyloid-ß (Aß) peptides occurs at residues 244-272 of apoE and residues 12-28 of Aß. ApoE4 has been implicated in promoting Aß deposition and impairing clearance of Aß. We hypothesized that blocking the apoE/Aß interaction would serve as an effective new approach to AD therapy. We have previously shown that treatment with Aß12-28P can reduce amyloid plaques in APP/PS1 transgenic (Tg) mice and vascular amyloid in TgSwDI mice with congophilic amyloid angiopathy. In the present study, we investigated whether the Aß12-28P elicits a therapeutic effect on tau-related pathology in addition to amyloid pathology using old triple transgenic AD mice (3xTg, with PS1M146V , APPSwe and tauP30IL transgenes) with established pathology from the ages of 21 to 26 months. We show that treatment with Aß12-28P substantially reduces tau pathology both immunohistochemically and biochemically, as well as reducing the amyloid burden and suppressing the activation of astrocytes and microglia. These affects correlate with a behavioral amelioration in the treated Tg mice.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Apolipoproteínas E
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Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Proteínas tau
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Enfermedad de Alzheimer
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Amiloidosis
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos