Cited by 374Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer’s disease

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Ferreira, Sergio T., Lourenco, Mychael V., Oliveira, Mauricio M., De Felice, Fernanda G.·2015·Frontiers in Cellular Neuroscience

Abstract

Alzheimer's disease (AD) is the most common form of dementia in the elderly, and affects millions of people worldwide. As the number of AD cases continues to increase in both developed and developing countries, finding therapies that effectively halt or reverse disease progression constitutes a major research and public health challenge. Since the identification of the amyloid-β peptide (Aβ) as the major component of the amyloid plaques that are characteristically found in AD brains, a major effort has aimed to determine whether and how Aβ leads to memory loss and cognitive impairment. A large body of evidence accumulated in the past 15 years supports a pivotal role of soluble Aβ oligomers (AβOs) in synapse failure and neuronal dysfunction in AD. Nonetheless, a number of basic questions, including the exact molecular composition of the synaptotoxic oligomers, the identity of the receptor(s) to which they bind, and the signaling pathways that ultimately lead to synapse failure, remain to be definitively answered. Here, we discuss recent advances that have illuminated our understanding of the chemical nature of the toxic species and the deleterious impact they have on synapses, and have culminated in the proposal of an Aβ oligomer hypothesis for Alzheimer's pathogenesis. We also highlight outstanding questions and challenges in AD research that should be addressed to allow translation of research findings into effective AD therapies.

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Crossref · 10.3389/fncel.2015.00191

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  • SCFAs interfere with protein-protein interactions between amyloid-β peptides, disrupting their assembly into neurotoxic oligomers, the main toxins responsible for synapse dysfunction and cognitive deficits in AD.

    “It is worth noting that SCFAs interfere with protein-protein interactions between amyloid-β peptides (Aβ), thereby disrupting their assembly into neurotoxic oligomers (34), the main toxins responsible for synapse dysfunction and cognitive deficits in AD (164).”

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Authors
Ferreira, S. T., Lourenco, M. V., Oliveira, M. M., & De Felice, F. G.
Affiliations
Universidade Federal do Rio de Janeiro (BR)
Corresponding author
Ferreira, Sergio T.
Venue
Frontiers in Cellular Neuroscience
Published
2015-05-26
Volume
9
Pages
191-191
ISSN
1662-5102 (ISSN-L)
OpenAlex
W1520284233
Cited by
373
References
254
Citations by year
2026: 23 · 2025: 24 · 2024: 16 · 2023: 40 · 2022: 38 · 2021: 51 · 2020: 45 · 2019: 33 · 2018: 40 · 2017: 38 · 2016: 23 · 2015: 2
FWCI
4.22
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
  • Institute for Translational Neuroscience
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid-beta oligomers, synaptotoxicity, cognitive impairment, amyloid plaques, neuronal dysfunction, memory loss, Alzheimer's disease pathogenesis, Alzheimer's disease treatment

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