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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; Srivatsan, Subhashini; Qingli Xiao; Lefton, Katheryn B.; Yamada, Kaoru; Mahan, Thomas E.; Jin-Moo Lee; Shaw, Andrey S.; Holtzman, David M.
- 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.
- Subjects
AMYLOID genetics; AMYLOID beta-protein; ALZHEIMER'S disease; GLYCOPROTEINS; HYPOPROTEINEMIA
- Publication
Molecular Neurodegeneration, 2015, Vol 10, Issue 1, p1
- ISSN
1750-1326
- Publication type
Article
- DOI
10.1186/s13024-015-0006-y