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Cited by 116Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Transcriptome analysis of synaptoneurosomes identifies neuroplasticity genes overexpressed in incipient Alzheimer's disease

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Williams, Celia, Mehrian Shai, Ruty, Wu, Yongchun, Hsu, Ya-Hsuan, Sitzer, Traci, Spann, Bryan, McCleary, Carol, Mo, Yi +1 more·2009·PLoS ONE
DOI 10.1371/journal.pone.0004936PMC PMC2654156
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Abstract

In Alzheimer's disease (AD), early deficits in learning and memory are a consequence of synaptic modification induced by toxic beta-amyloid oligomers (oAbeta). To identify immediate molecular targets downstream of oAbeta binding, we prepared synaptoneurosomes from prefrontal cortex of control and incipient AD (IAD) patients, and isolated mRNAs for comparison of gene expression. This novel approach concentrates synaptic mRNA, thereby increasing the ratio of synaptic to somal mRNA and allowing discrimination of expression changes in synaptically localized genes. In IAD patients, global measures of cognition declined with increasing levels of dimeric Abeta (dAbeta). These patients also showed increased expression of neuroplasticity related genes, many encoding 3'UTR consensus sequences that regulate translation in the synapse. An increase in mRNA encoding the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) was paralleled by elevated expression of the corresponding protein in IAD. These results imply a functional impact on synaptic transmission as GluR2, if inserted, maintains the receptors in a low conductance state. Some overexpressed genes may induce early deficits in cognition and others compensatory mechanisms, providing targets for intervention to moderate the response to dAbeta.

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  • The increase in GluR2 AMPA receptor subunits would be expected to result in increased spine head diameter, which could explain observations in PS19 hippocampal spines.

    “The increase in GluR2 AMPA receptor subunits would be expected to result in increased spine head diameter, which could explain our observations in PS19 hippocampal spines.”

    From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Williams et al., 2009

    The Results section (“Expression of GluR2 mRNA and corresponding protein”; page unavailable) reports increased GluR2 receptor subunits in synaptoneurosomes from patients with incipient Alzheimer’s disease. The Discussion section (“GluR2 subunit regulation, oAβ and neuroplasticity”; page unavailable) does not say that increased GluR2 would enlarge spine heads. The PS19 observations are the citing authors’ own, but the proposed explanation for them is not established by this source. (LLM, conf=0.85)

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Authors
Williams, C., Mehrian Shai, R., Wu, Y., Hsu, Y.-H., Sitzer, T., Spann, B., McCleary, C., Mo, Y., & Miller, C. A.
Affiliations
University of Southern California (US)
Corresponding author
  • Williams, Celia
  • Wu, Yongchun
  • Hsu, Ya-Hsuan
  • Sitzer, Traci
  • Spann, Bryan
  • McCleary, Carol
  • Mo, Yi
  • Miller, Carol A.
ORCID
Spann, Bryan
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2009-03-19
Volume
4
Issue
3
Pages
e4936
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0004936
PMC
PMC2654156
OpenAlex
W1995550632
Cited by
116
References
13
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 10 · 2020: 5 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 11 · 2013: 7 · 2012: 13
FWCI
6.31
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • University of Southern California
  • National Institute on Aging (P50AG005142)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, synaptoneurosomes, amyloid-beta oligomers, prefrontal cortex, GluR2, AMPA receptors, translational regulation, cognitive decline, synaptic transmission
MeSH terms
Alzheimer Disease, Cognition, Humans, Neuronal Plasticity, Neurons, Neuropsychological Tests, RNA, Messenger, Synapses, Synaptosomes, Cluster Analysis, Amyloid beta-Peptides, Prefrontal Cortex, Receptors, AMPA, Disease Progression, Gene Expression Profiling, Receptor, Muscarinic M3, Microarray Analysis

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