title: Mercury-induced amyloid-beta (Aβ) accumulation in the brain is mediated by disruption of Aβ transport.
abstract: According to a recent study, mercury (Hg) exposure contributes to Alzheimer's disease (AD). However, the underlying mechanisms are not understood. This study investigated the effect of methylmercury (MeHg) treatment on the generation, degradation, and transport of amyloid β-protein (Aβ) in the brain. Wistar rats were administered MeHg by gavage (0, 20, 200, and 2,000 μg Hg/kg/day) for 4 weeks. The total Hg in the blood and brain regions was measured, and the levels of Aβ42 in plasma, cerebrospinal fluid (CSF), and brain regions were estimated. The expression of amyloid precursor protein (APP), beta-site APP-cleaving enzyme 1 (BACE1), and neprilysin (NEP) in the brain regions was determined, in addition to the expression of low-density lipoprotein receptor-related protein 1 (LRP1) and the receptor for advanced glycation end products (RAGE) in the brain capillary endothelium (BCE). Finally, the amount of soluble low-density lipoprotein receptor-related protein (sLRP) in the plasma was determined. Aβ42 levels were decreased in the CSF of the 2,000 μg Hg/kg/day group compared with controls, and Aβ42 levels increased in the hippocampus (HC) in a dose-dependent manner. MeHg decreased LRP1 expression but increased RAGE levels in BCE. sLRP levels were decreased in the plasma of the MeHg-treated rats. They were positively correlated with CSF Aβ42 and negatively correlated with Aβ42 and Hg levels in HC. These results imply that MeHg reduces the transportation of Aβ, thereby resulting in the accumulation of the protein in the HC. Plasma sLRP levels may be an early biomarker of Hg-induced Aβ accumulation in the brain.
authors: Department of Preventive Medicine, College of Medicine, Chung-Ang University.
authors: Dong-Kyeong
authors: DK
authors: Kim
authors: Jung-Duck
authors: JD
authors: Park
authors: Byung-Sun
authors: BS
authors: Choi
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D015260:Neprilysin / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects*; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008767:Methylmercury Compounds; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; D015260:Neprilysin