Cited by 61Alzheimer's disease research and treatmentsParkinson's Disease Mechanisms and TreatmentsDementia and Cognitive Impairment Research

Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits

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Larson, Megan E., Greimel, Susan J., Amar, Fatou, LaCroix, Michael, Boyle, Gabriel, Sherman, Mathew A., Schley, Hallie, Miel, Camille +6 more·2017·Proceedings of the National Academy of Sciences

Abstract

Significance: Alzheimer’s disease (AD) is the most common form of dementia affecting an estimated 5.3 million Americans based on the 2015 Report of the Alzheimer Association. Our current understanding of the pathogenesis of AD suggests that soluble, nonfibrillar forms of amyloid proteins [e.g. amyloid-β, tau, and α-synuclein (αSyn)] may be responsible for impairing cognition and have therefore been advanced to be the most bioactive species in this brain disorder. We sought to determine the potential contribution of αSyn oligomers to AD-associated cognitive decline. We found that selective αSyn oligomers are elevated in AD brains and that genetically elevating oligomeric αSyn in an AD mouse model led to a selective decrease in presynaptic proteins and cognitive performance.

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Crossref · 10.1073/pnas.1704698114

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  • Soluble αSyn and the local concentrations thereof may play an important role in Alzheimer's disease regardless of Lewy-related pathology.

    “the results provided by Larson and colleagues [69, 73] suggest that soluble αSyn and the local concentrations thereof may play an important role in AD regardless of LRP.”

    From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [73]

  • Post-mortem Alzheimer's disease brains without detectable Lewy-related pathology have significantly increased levels of intracellular soluble αSyn monomers and oligomers in the inferior temporal lobe.

    “two reports from Larson, Lesné and co-workers demonstrated significantly increased levels of intracellular soluble αSyn monomers and oligomers in the inferior temporal lobe of AD brains without any detectable LRP [69, 73].”

    From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [73]

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Authors
Larson, M. E., Greimel, S. J., Amar, F., LaCroix, M., Boyle, G., Sherman, M. A., Schley, H., Miel, C., Schneider, J. A., Kayed, R., Benfenati, F., Lee, M. K., Bennett, D. A., & Lesné, S. E.
Affiliations
  • University of Minnesota (US)
  • Rush University Medical Center (US)
  • The University of Texas Medical Branch at Galveston (US)
  • Italian Institute of Technology (IT)
Venue
Proceedings of the National Academy of Sciences
Published
2017-05-22
Volume
114
Issue
23
Pages
E4648-E4657
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2618220838
Cited by
61
References
81
Citations by year
2026: 2 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 3 · 2019: 14 · 2018: 8 · 2017: 3
FWCI
5.66
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
Funders
  • HHS | NIH | National Institute on Aging (R01AG044342, P30AG10161, R01AG15819)
  • University of Minnesota Foundation (4185-9227-14)
  • HHS | NIH | National Institute of Neurological Disorders and Stroke (R01NS094557)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
alpha-synuclein oligomers, synapsin, Alzheimer's disease, memory impairment, cognitive decline, presynaptic proteins, transgenic mouse model, presynaptic dysfunction
MeSH terms
Alzheimer Disease, Animals, Brain, Cognition, Disease Models, Animal, Humans, Memory Disorders, Mice, Transgenic, Nuclear Proteins, Recombinant Proteins, Solubility, Genes, Tumor Suppressor, Synapsins, Cyclic AMP Response Element-Binding Protein, Protein Structure, Quaternary, Mice, alpha-Synuclein, Nuclear Receptor Subfamily 4, Group A, Member 2

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