Gangliosides as a possible therapeutic target for Alzheimer’s disease
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AbstractBackground

Gangliosides are known to play an important role in Alzheimer’s disease (AD), although the exact mechanism remains unclear.

Methods

To study the role of gangliosides in AD, we crossed st3gal5-deficicent (ST3 -/-) mice that lack major brain gangliosides with 5xFAD mice to have ST3-/- 5xFAD animals. We compared Aβ accumulation, level of neuroinflammation, and cognitive skills. To further confirm the role of sialylated gangliosides as a possible target for AD therapy, we treated wild type (WT) 5xFAD mice with Limax flavus agglutinin (LFA), a sialic-acid specific lectin.

Results

5xFAD ST3 -/- mice had 2-fold (8 month-old) and 3-fold (12 month-old) lower burdens of amyloid depositions when compared to WT 5xFAD mice. 5xFAD ST3 -/- mice also exhibit lower degree of neuroinflammation and better performance on cognitive Barnes Maze test that aged-matched WT 5xFAD animals. We also demonstrated that LFA administration reversed the progression of AD as confirmed by a) reduced neuroinflammation, b) reduced amyloid deposition, and c) improved cognitive functions.

Conclusions

Here, we have presented new data demonstrating that sialylated gangliosides play an important role of the pathophysiology in AD, and as a possible therapeutic target for AD.
Acceptance Date04/09/2018
All Author(s) ListThomas L.B Lau, Marina Dukhinova, Ekaterina Kopeikina, Amanda W.Y. Yung, Eugene D. Ponomarev
Name of ConferenceInternational Alzheimer’s Disease Conference 2018
Start Date of Conference07/09/2018
End Date of Conference08/09/2018
Place of ConferenceHong Kong
Country/Region of ConferenceHong Kong
Year2018
Month9
LanguagesEnglish-United States
Keywordsgangliosides, AD, neuroinflammation

Last updated on 2018-19-10 at 11:51