title: NDP52 associates with phosphorylated tau in brains of an Alzheimer disease mouse model.
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 (Aβ) 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 Aβ, but not with the extracellular Aβ 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.
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chungju-si, Chungcheongbuk-do 363-951, Republic of Korea.
authors.forename: Sunhyo
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chungju-si, Chungcheongbuk-do 363-951, Republic of Korea.
authors.forename: Daehoon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chungju-si, Chungcheongbuk-do 363-951, Republic of Korea.
authors.forename: Jae Chun
authors.initials: JC
authors.lastname: Song
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chungju-si, Chungcheongbuk-do 363-951, Republic of Korea.
authors.forename: Sun-Jung
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chungju-si, Chungcheongbuk-do 363-951, Republic of Korea.
authors.forename: Sang-Moon
authors.initials: SM
authors.lastname: Yun
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chungju-si, Chungcheongbuk-do 363-951, Republic of Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Koh
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chungju-si, Chungcheongbuk-do 363-951, Republic of Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, University of Rochester Medical Center, University of Rochester, 601 Elmwood Ave., Rochester, NY, USA.
authors.forename: Gail V W
authors.initials: GV
authors.lastname: Johnson
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Chungju-si, Chungcheongbuk-do 363-951, Republic of Korea. Electronic address: chulman67@gmail.com.
authors.forename: Chulman
authors.initials: C
authors.lastname: Jo
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014018:Tissue Distribution; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C480860:Map1lc3b protein, mouse; C558298:Mapt protein, mouse; D008869:Microtubule-Associated Proteins; C000597434:NDP52 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D016875:tau Proteins
keywords: Alzheimer’s disease; Autophagy; Autophagy receptor; LC3; NDP52; Tau