Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life.
Nat Neurosci
; 23(12): 1580-1588, 2020 12.
Article
en En
| MEDLINE
| ID: mdl-33199898
ABSTRACT
Amyloid-ß (Aß) deposits are a relatively late consequence of Aß aggregation in Alzheimer's disease. When pathogenic Aß seeds begin to form, propagate and spread is not known, nor are they biochemically defined. We tested various antibodies for their ability to neutralize Aß seeds before Aß deposition becomes detectable in Aß precursor protein-transgenic mice. We also characterized the different antibody recognition profiles using immunoprecipitation of size-fractionated, native, mouse and human brain-derived Aß assemblies. At least one antibody, aducanumab, after acute administration at the pre-amyloid stage, led to a significant reduction of Aß deposition and downstream pathologies 6 months later. This demonstrates that therapeutically targetable pathogenic Aß seeds already exist during the lag phase of protein aggregation in the brain. Thus, the preclinical phase of Alzheimer's disease-currently defined as Aß deposition without clinical symptoms-may be a relatively late manifestation of a much earlier pathogenic seed formation and propagation that currently escapes detection in vivo.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Precursor de Proteína beta-Amiloide
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Enfermedad de Alzheimer
Límite:
Aged
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Aged80
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Animals
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Nat Neurosci
Asunto de la revista:
NEUROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania