Cited by 127Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchLysosomal Storage Disorders Research

Elimination of GD3 synthase improves memory and reduces amyloid-β plaque load in transgenic mice

Bernardo, Alexandra, Harrison, Fiona E., McCord, Meghan, Zhao, Jiali, Bruchey, Aleksandra, Davies, Sean S., Jackson Roberts, L., Mathews, Paul M. +5 more·2009·Neurobiology of Aging

Abstract

Gangliosides have been shown to be necessary for beta-amyloid (Abeta) binding and aggregation. GD3 synthase (GD3S) is responsible for biosynthesis of the b- and c-series gangliosides, including two of the four major brain gangliosides. We examined Abeta-ganglioside interactions in neural tissue from mice lacking the gene coding for GD3S (St8sia1), and in a double-transgenic (APP/PSEN1) mouse model of Alzheimer's disease cross-bred with GD3S-/- mice. In primary neurons and astrocytes lacking GD3S, Abeta-induced cell death and Abeta aggregation were inhibited. Like GD3S-/- and APP/PSEN1 double-transgenic mice, APP/PSEN1/GD3S-/- "triple-mutant" mice are indistinguishable from wild-type mice on casual examination. APP/PSEN1 double-transgenics exhibit robust impairments on a number of reference-memory tasks. In contrast, APP/PSEN1/GD3S-/- triple-mutant mice performed as well as wild-type control and GD3S-/- mice. Consistent with the behavioral improvements, both aggregated and unaggregated Abeta and associated neuropathology were almost completely eliminated in triple-mutant mice. These results suggest that GD3 synthase may be a novel therapeutic target to combat the cognitive deficits, amyloid plaque formation, and neurodegeneration that afflict Alzheimer's patients.

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Crossref · 10.1016/j.neurobiolaging.2007.12.022

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Authors
Bernardo, A., Harrison, F. E., McCord, M., Zhao, J., Bruchey, A., Davies, S. S., Jackson Roberts, L., Mathews, P. M., Matsuoka, Y., Ariga, T., Yu, R. K., Thompson, R., & McDonald, M. P.
Affiliations
  • Vanderbilt University (US)
  • Nathan Kline Institute for Psychiatric Research (US)
  • Georgetown University (US)
  • Augusta University (US)
  • University of Tennessee Health Science Center (US)
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2009-11
Volume
30
Issue
11
Pages
1777-1791
ISSN
0197-4580 (ISSN-L)
OpenAlex
W1974394119
Cited by
127
References
95
Citations by year
2026: 4 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 10 · 2021: 9 · 2020: 7 · 2019: 6 · 2018: 13 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 9 · 2013: 6 · 2012: 9
FWCI
5.64
Type
journal article
Language
en
Open access
closed
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (R01AG023597, R01AG022439, AG022455, AG023597, K01AG022455, AG-022439)
  • National Institute of General Medical Sciences (GM 42056)
  • National Institute of Neurological Disorders and Stroke (NS04520, R21NS043581)
  • H2020 European Research Council
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
GD3 synthase, ST8SIA1, gangliosides, amyloid-beta, amyloid plaques, Alzheimer's disease, memory impairment, amyloid fibril formation, neurodegeneration, astrocytes, neurons, therapeutic target
MeSH terms
Alzheimer Disease, Amyloid, Animals, Cells, Cultured, Cerebral Cortex, Disease Models, Animal, Humans, Gas Chromatography-Mass Spectrometry, Memory, Memory Disorders, Mice, Transgenic, Mutation, Neurons, Protein Binding, Sialyltransferases, Lipid Peroxidation, Amyloid beta-Protein Precursor, Maze Learning, CD11b Antigen, Mice, Presenilin-1, Plaque, Amyloid

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