Major brain ganglioside-deficient 5XFAD mice exhibit a reduced level of amyloid depositions, diminished activation of microglia, improved neuronal survival, and intact cognitive abilities
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AbstractBackground
Although it was suggested that gangliosides play an important role in the binding of amyloid fragments to neuronal cells, the exact role of gangliosides in Alzheimer’s disease (AD) pathology remains unclear.
Methods
To understand the role of gangliosides in AD pathology in vivo we crossed st3gal5-deficient (ST3-/-) mice that lack of major brain gangliosides GM1, GD1a, GD3, GT1b and GQ1b with 5XFAD transgenic mice that overexpress three mutant human amyloid proteins AP695 and two presenilin PS1 genes.
Results
We found that ST3-deficient 5XFAD mice have a significantly reduced burden of amyloid depositions, low level of neuroinflammation, and did not exhibit neuronal loss or synaptic dysfunction. ST3-/- 5XFAD mice performed significantly better in a cognitive test than wild-type (WT) 5XFAD mice, which was comparable with WT non-transgenic mice. Treatment of WT 5XFAD mice with the sialic acid-specific Limax flavus agglutinin resulted in substantial improvement of AD pathology to a level of ST3-/- 5XFAD mice.
Conclusion
Our findings highlight an important role for gangliosides as a target for the treatment of AD.
Reference
Dukhinova M., Veremeyko T., Yung A.W.Y., Kuznetsova I.S., Lau T.Y.B., Kopeikina E., Chan A.M.L., Ponomarev E.D. (2019). Fresh evidence for major brain gangliosides as a target for the treatment of Alzheimer's disease. Neurobiol Aging.77: 128-143.
Acceptance Date31/05/2019
All Author(s) ListMarina DUKHINOVA, Tatyana VEREMEYKO, Amanda W.Y. YUNG, Inna S. KUZNETSOVA, Thomas Y.B. LAU, Andrew M.L. CHAN, Eugene D. PONOMAREV
Name of ConferenceInternational Alzheimer’s Disease Conference 2019
Start Date of Conference31/05/2019
End Date of Conference01/06/2019
Place of Conference12W, Science Park, Shatin, Hong Kong
Country/Region of ConferenceHong Kong
Year2019
Month5
Day31
LanguagesEnglish-United Kingdom
KeywordsAlzhemer's disease, gangliosides, neuronal lipid rafts, neuroinflammation

Last updated on 2019-05-06 at 10:18