Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model.
Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model.
复制标题
DOI：
10.1186/s13024-015-0006-y
复制
发表时间：
2015-03-19
影响因子：
15.1
通讯作者：
Holtzman DM
中科院分区：
文献类型：
--
作者：
Liao F;Jiang H;Srivatsan S;Xiao Q;Lefton KB;Yamada K;Mahan TE;Lee JM;Shaw AS;Holtzman DM
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. 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. 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.
登录
查看更多内容
影响因子：
15.1
作者：
Liao, Fan;Zhang, Tony J.;Mahan, Thomas E.;Jiang, Hong;Holtzman, David M.
通讯作者：
Holtzman, David M.
影响因子：
29
作者：
Shulman, Joshua M.;Chen, Kewei;Keenan, Brendan T.;Chibnik, Lori B.;Fleisher, Adam;Thiyyagura, Pradeep;Roontiva, Auttawut;McCabe, Cristin;Patsopoulos, Nikolaos A.;Corneveaux, Jason J.;Yu, Lei;Huentelman, Matthew J.;Evans, Denis A.;Schneider, Julie A.;Reiman, Eric M.;De Jager, Philip L.;Bennett, David A.
通讯作者：
Bennett, David A.
DOI：
10.1523/jneurosci.5845-11.2012
发表时间：
2012-03-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bero AW;Bauer AQ;Stewart FR;White BR;Cirrito JR;Raichle ME;Culver JP;Holtzman DM
通讯作者：
Holtzman DM
影响因子：
56.9
作者：
LEVYLAHAD, E;WASCO, W;TANZI, RE
通讯作者：
TANZI, RE
影响因子：
16.6
作者：
Dimitrov, Mitko;Alattia, Jean-Rene;Fraering, Patrick C.
通讯作者：
Fraering, Patrick C.