title: Sodium Chloride Increases Aβ Levels by Suppressing Aβ Clearance in Cultured Cells.
abstract: Recent studies suggest that high-salt diet is associated with cognitive decline in human and mouse. The fact that genetic factors account for less than 50% cases of sporadic Alzheimer's disease (AD) highlights the important contribution of environmental factors, such as high-salt diet, in AD pathogenesis. However, whether and how high-salt diet fits the "amyloid cascade" hypothesis remains unexplored. Here, we show sodium chloride (NaCl) could increase Aβ levels in the medium of HEK293 cells overexpressing amyloid precursor protein (APP) or C99 fragment. NaCl treatment dose not affect APP level, gamma secretase level or activity. Instead, NaCl treatment suppresses the capacity of cells to clear Aβ and reduces Apolipoprotein E (ApoE) level. Finally, NaCl treated THP-1 or BV2 cells are inefficient in clearing Aβ when co-cultured with rat primary neurons. Our study suggests that high-salt diet may increase AD risk by directly modulating Aβ levels.
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Cheng
authors.affiliation: Department of Neurology & Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Neurology, First People's Hospital of Yunnan Province affiliated to Kunming University of Science and Technology, Kunming, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yu-Wu
authors.initials: YW
authors.lastname: Zhao
authors.affiliation: School of Life Sciences and Technology, Tongji University. East Hospital Affiliated To Tongji University, Shanghai, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Cheng
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004032:Diet; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D012965:Sodium Chloride; D053829:Amyloid Precursor Protein Secretases