The amyloid cascade hypothesis: an updated critical review.
Brain
; 146(10): 3969-3990, 2023 10 03.
Article
em En
| MEDLINE
| ID: mdl-37183523
ABSTRACT
Results from recent clinical trials of antibodies that target amyloid-ß (Aß) for Alzheimer's disease have created excitement and have been heralded as corroboration of the amyloid cascade hypothesis. However, while Aß may contribute to disease, genetic, clinical, imaging and biochemical data suggest a more complex aetiology. Here we review the history and weaknesses of the amyloid cascade hypothesis in view of the new evidence obtained from clinical trials of anti-amyloid antibodies. These trials indicate that the treatments have either no or uncertain clinical effect on cognition. Despite the importance of amyloid in the definition of Alzheimer's disease, we argue that the data point to Aß playing a minor aetiological role. We also discuss data suggesting that the concerted activity of many pathogenic factors contribute to Alzheimer's disease and propose that evolving multi-factor disease models will better underpin the search for more effective strategies to treat the disease.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article