title: Detection of misfolded Aβ oligomers for sensitive biochemical diagnosis of Alzheimer's disease.
abstract: Alzheimer's disease (AD) diagnosis is hampered by the lack of early, sensitive, and objective laboratory tests. We describe a sensitive method for biochemical diagnosis of AD based on specific detection of misfolded Aβ oligomers, which play a central role in AD pathogenesis. The protein misfolding cyclic amplification assay (Aβ-PMCA), exploits the functional property of Aβ oligomers to seed the polymerization of monomeric Aβ. Aβ-PMCA allowed detection of as little as 3 fmol of Aβ oligomers. Most importantly, using cerebrospinal fluid, we were able to distinguish AD patients from control individuals affected by a variety of other neurodegenerative disorders or nondegenerative neurological diseases with overall sensitivity of 90% and specificity of 92%. These findings provide the proof-of-principle basis for developing a highly sensitive and specific biochemical test for AD diagnosis.
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Salvadores
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahnawaz
authors.affiliation: Neurology Unit, Università di Milano, Centro Dino Ferrari, Fondazione Ca' Granda, IRCC Ospedale Policlinico, via F. Sforza 35, 20122 Milan, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.affiliation: IRCCS Foundation "Carlo Besta" Neurological Institute, Via Celoria 11, 20133 Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA. Electronic address: claudio.soto@uth.tmc.edu.
authors.forename: Claudio
authors.initials: C
authors.lastname: Soto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000378:metabolism*; D015415:Biomarkers; D016022:Case-Control Studies; D006801:Humans; D008875:Middle Aged; D066329:Protein Aggregates; D017510:Protein Folding
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D066329:Protein Aggregates