title: FAD mutants unable to increase neurotoxic Abeta 42 suggest that mutation effects on neurodegeneration may be independent of effects on Abeta.
abstract: Strong support for a primary causative role of the Abeta peptides in the development of Alzheimer's disease (AD) neurodegeneration derives from reports that presenilin familial AD (FAD) mutants alter amyloid precursor protein processing, thus increasing production of neurotoxic Abeta 1-42 (Abeta 42). This effect of FAD mutants is also reflected in an increased ratio of peptides Abeta 42 over Abeta 1-40 (Abeta 40). In the present study, we show that several presenilin 1 FAD mutants failed to increase production of Abeta 42 or the Abeta 42/40 ratio. Our data suggest that the mechanism by which FAD mutations promote neurodegeneration and AD may be independent of their effects on Abeta production.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shioi
authors.forename: Anastasios
authors.initials: A
authors.lastname: Georgakopoulos
authors.forename: Pankaj
authors.initials: P
authors.lastname: Mehta
authors.forename: Zen
authors.initials: Z
authors.lastname: Kouchi
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Litterst
authors.forename: Lia
authors.initials: L
authors.lastname: Baki
authors.forename: Nikolaos K
authors.initials: NK
authors.lastname: Robakis
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009154:Mutation / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D053764:Presenilin-1 / Q000235:genetics* / Q000502:physiology; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)