title: In cerebrospinal fluid ER chaperones ERp57 and calreticulin bind beta-amyloid.
abstract: The beta-amyloids (abetas) are the major components of the plaque observed in the brains of patients with Alzheimer's disease. The conundrum is that although they are produced in everyone during the posttranslational processing in the endoplasmic reticulum (ER) of the amyloid precursor protein (APP), deposits are only observed in the elderly. Our work suggests that normals have a carrier protein(s) keeping them in solution. Based on immunoblotting studies of cerebrospinal fluid (CSF) from normals, we find that the bulk of the abetas are bound to the ER chaperones, ERp57 and calreticulin, suggesting that these may be carrier proteins which prevent aggregation of the abetas and that the deposits are due to faulty ER posttranslational processing of APP with the failure to form this complex. If membrane protein synthesis is similarly affected, it could explain the neuronal dysfunction characteristic of Alzheimer's disease.
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Erickson
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Dunning
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Olson
authors.forename: Sheftel J
authors.initials: SJ
authors.lastname: Cohen
authors.forename: Alan T
authors.initials: AT
authors.lastname: Davis
authors.forename: W Gibson
authors.initials: WG
authors.lastname: Wood
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Holtzman
mesh_terms: D000375:Aging / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D037282:Calreticulin / Q000134:cerebrospinal fluid*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000134:cerebrospinal fluid*; D006801:Humans; D007535:Isomerases / Q000134:cerebrospinal fluid*; D018832:Molecular Chaperones / Q000134:cerebrospinal fluid*; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases
chemical_list: D016229:Amyloid beta-Peptides; D037282:Calreticulin; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human