Why have all amyloid cascade-targeting drugs failed despite strong mechanistic rationale?

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Description

The abstract notes that all drugs developed to inhibit the amyloid pathway have failed, creating a contradiction between the established amyloid cascade hypothesis and therapeutic outcomes. This failure suggests missing pathogenic mechanisms or flawed therapeutic targets.

Gap type: contradiction Source paper: Intracellular Calcium Dysregulation by the Alzheimer’s Disease-Linked Protein Presenilin 2. (2020, International journal of molecular sciences, PMID:31991578)

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