title: Amyloid-β peptides are generated in mitochondria-associated endoplasmic reticulum membranes.
abstract: Extracellular aggregates of amyloid-β peptides (Aβ) are a hallmark in Alzheimer's disease (AD) brains. Recent findings suggest that Aβ is generated intracellularly and potential production sites include endosomes and trans-Golgi network. We determined the production of Aβ in subcellular fractions isolated from mouse brain. We found that a considerable amount of Aβ is produced at mitochondria-endoplasmic reticulum (ER) contact sites including outer mitochondrial membrane and mitochondria-associated ER membranes. Enhanced Aβ production at this site may disturb ER, mitochondrial and mitochondria-ER contact site function. This may be one key step in the cascade of events eventually leading to neurodegeneration in AD.
authors.affiliation: Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Stockholm, Sweden.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Schreiner
authors.affiliation: Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Stockholm, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Hedskog
authors.affiliation: Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Stockholm, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Wiehager
authors.affiliation: Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Ankarcrona
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000648:ultrastructure*; D027682:Cation Transport Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000648:ultrastructure
chemical_list: D016229:Amyloid beta-Peptides; D027682:Cation Transport Proteins; D003576:Electron Transport Complex IV; C526871:cytochrome c oxidase subunit I, mouse; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase
keywords: Alzheimer's disease; endoplasmic reticulum (ER); intracellular amyloid-β peptides; mitochondria; mitochondria-ER contact sites; mitochondria-associated ER membranes (MAM)