First Author | Liao F | Year | 2015 |
Journal | Mol Neurodegener | Volume | 10 |
Pages | 12 | PubMed ID | 25887956 |
Mgi Jnum | J:323141 | Mgi Id | MGI:6843865 |
Doi | 10.1186/s13024-015-0006-y | Citation | Liao F, et al. (2015) Effects of CD2-associated protein deficiency on amyloid-beta in neuroblastoma cells and in an APP transgenic mouse model. Mol Neurodegener 10:12 |
abstractText | 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-beta (Abeta) in the brain. In humans, CD2AP AD susceptibility locus (rs9349407) is associated with an increased plaque burden. Abeta 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 Abeta 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 Abeta release and a lower Abeta42/Abeta40 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 Abeta42/Abeta40 ratio in brain tissue lysates while there was no effect on Abeta deposition or accumulation in PS1APP mice expressing one copy of CD2AP. CONCLUSION: CD2-Associated Protein affects Abeta levels and Abeta42/Abeta40 ratio in vitro. The effect of CD2-Associated Protein on Abeta metabolism is subtle in vivo. |