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Open Access 01-12-2015 | Research article

Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model

Authors: Fan Liao, Hong Jiang, Subhashini Srivatsan, Qingli Xiao, Katheryn B Lefton, Kaoru Yamada, Thomas E Mahan, Jin-Moo Lee, Andrey S Shaw, David M Holtzman

Published in: Molecular Neurodegeneration | Issue 1/2015

Abstract

Background

CD2-associated protein (CD2AP) is an SH3-containing scaffold adaptor protein which regulates the actin cytoskeleton. Recently, CD2AP was identified as a genetic risk factor for Alzheimer’s disease (AD) by several genome-wide association studies. One of the hallmarks of AD is the accumulation of aggregated forms of Amyloid-β (Aβ) in the brain. In humans, CD2AP AD susceptibility locus (rs9349407) is associated with an increased plaque burden. Aβ production is highly regulated by endocytosis and is influenced by lysosomal function. Lysosomal trafficking is influenced by CD2AP. In this study, we decreased CD2AP levels in N2a neuroblastoma cultures and PS1APP mice and analyzed Aβ levels and plaque burden.

Results

Our data show that suppressing CD2AP expression using shRNA in N2a-APP695 cells results in decreased cell membrane amyloid precursor protein, decreased Aβ release and a lower Aβ₄₂/Aβ₄₀ ratio. CD2AP protein is expressed in the brain as detected by western blot, and the expression level is dependent on gene dosage. In 1-month old PS1APP mice, complete loss of CD2AP in brain resulted in a decreased Aβ₄₂/Aβ₄₀ ratio in brain tissue lysates while there was no effect on Aβ deposition or accumulation in PS1APP mice expressing one copy of CD2AP.

Conclusion

CD2-Associated Protein affects Aβ levels and Aβ₄₂/Aβ₄₀ ratio in vitro. The effect of CD2-Associated Protein on Aβ metabolism is subtle in vivo.

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Title: Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model
Authors: Fan Liao
Hong Jiang
Subhashini Srivatsan
Qingli Xiao
Katheryn B Lefton
Kaoru Yamada
Thomas E Mahan
Jin-Moo Lee
Andrey S Shaw
David M Holtzman
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2015
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/s13024-015-0006-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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