Ageing Research Reviews

Alzheimer's Disease as Progressive Failure of Dynamic Memory Architecture and Conscious Integration

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Abstract

Anti-amyloid antibodies substantially reduce amyloid plaque burden, yet the resulting cognitive benefit remains modest, exposing a limitation in the conventional storage-and-deletion model of memory. We propose that Alzheimer's disease (AD) is better understood as a progressive failure of the dynamic processes that continuously reconstruct memory and bind it to conscious experience, rather than static deletion of stored content following synaptic loss. Amyloid-beta oligomers and mislocalized tau disrupt synaptic tagging, local dendritic protein synthesis, and retrieval-triggered reconsolidation well before synapses are structurally eliminated. Hippocampal sharp-wave ripples, theta-gamma coupling, and spindle-slow oscillation nesting form a shared infrastructure for memory consolidation and conscious access whose progressive failure constitutes memory failure and consciousness failure simultaneously. We trace this cascade from preclinical process dysregulation through autonoetic dissociation in mild cognitive impairment to hippocampal indexing collapse in dementia, and identify dynamic process biomarkers and therapeutic strategies, including sleep oscillation enhancement, closed-loop neurostimulation, and gamma entrainment, that the prevailing storage model cannot accommodate.

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