The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's disease

Sergio T. Ferreira, William L. Klein*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

273 Scopus citations

Abstract

Alzheimer's disease (AD) is the 3rd most costly disease and the leading cause of dementia. It can linger for many years, but ultimately is fatal, the 6th leading cause of death. Alzheimer's disease (AD) is fatal and affected individuals can sometimes linger many years. Current treatments are palliative and transient, not disease modifying. This article reviews progress in the search to identify the primary AD-causing toxins. We summarize the shift from an initial focus on amyloid plaques to the contemporary concept that AD memory failure is caused by small soluble oligomers of the Aβ peptide, toxins that target and disrupt particular synapses. Evidence is presented that links Aβ oligomers to pathogenesis in animal models and humans, with reference to seminal discoveries from cell biology and new ideas concerning pathogenic mechanisms, including relationships to diabetes and Fragile X. These findings have established the oligomer hypothesis as a new molecular basis for the cause, diagnosis, and treatment of AD.

Original languageEnglish (US)
Pages (from-to)529-543
Number of pages15
JournalNeurobiology of Learning and Memory
Volume96
Issue number4
DOIs
StatePublished - Nov 2011

Keywords

  • Alzheimer's disease
  • Diabetes
  • Fragile X
  • Neurodegeneration
  • Oligomer

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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