Biochemical and Biophysical Research Communications, 2014, 01, 196─201

NDP52 associates with phosphorylated tau in brains of an Alzheimer disease mouse model

Sunhyo Kim, Daehoon Lee, Jae Chun Song, Sun-Jung Cho, Sang-Moon Yun, Young Ho Koh, Jihyun Song, Gail V.W. Johnson, Chulman Jo

Abstract

We previously showed that NDP52 (also known as calcoco2) plays a role as an autophagic receptor for phosphorylated tau facilitating its clearance via autophagy. Here, we examined the expression and association of NDP52 with autophagy-regulated gene (ATG) proteins including LC3, as well as phosphorylated tau and amyloid-beta (Ab) in brains of an AD mouse model. NDP52 was expressed not only in neurons, but also in microglia and astrocytes. NDP52 co-localized with ATGs and phosphorylated tau as expected since it functions as an autophagy receptor for phosphorylated tau in brain. Compared to wild-type mice, the number of autophagic vesicles (AVs) containing NDP52 in both cortex and hippocampal regions was significantly greater in AD model mice. Moreover, the protein levels of NDP52 and phosphorylated tau together with LC3-II were also significantly increased in AD model mice, reflecting autophagy impairment in the AD mouse model. By contrast, a significant change in p62/SQSTM1 level was not observed in this AD mouse model. NDP52 was also associated with intracellular Ab, but not with the extracellular Ab of amyloid plaques. We conclude that NDP52 is a key autophagy receptor for phosphorylated tau in brain. Further our data provide clear evidence for autophagy impairment in brains of AD mouse model, and thus strategies that result in enhancement of autophagic flux in AD are likely to be beneficial.

• ISBN or ISSN: 0006-291X

• 본 연구는 질병관리본부 연구개발과제(과제번호 2013-NG62002-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2013-NG62002-00) by Research of Korea Centers for Disease Control and Prevention.