title: Aβ40 oligomers identified as a potential biomarker for the diagnosis of Alzheimer's disease.
abstract: Alzheimer's Disease (AD) is the most prevalent form of dementia worldwide, yet the development of therapeutics has been hampered by the absence of suitable biomarkers to diagnose the disease in its early stages prior to the formation of amyloid plaques and the occurrence of irreversible neuronal damage. Since oligomeric Aβ species have been implicated in the pathophysiology of AD, we reasoned that they may correlate with the onset of disease. As such, we have developed a novel misfolded protein assay for the detection of soluble oligomers composed of Aβ x-40 and x-42 peptide (hereafter Aβ40 and Aβ42) from cerebrospinal fluid (CSF). Preliminary validation of this assay with 36 clinical samples demonstrated the presence of aggregated Aβ40 in the CSF of AD patients. Together with measurements of total Aβ42, diagnostic sensitivity and specificity greater than 95% and 90%, respectively, were achieved. Although larger sample populations will be needed to confirm this diagnostic sensitivity, our studies demonstrate a sensitive method of detecting circulating Aβ40 oligomers from AD CSF and suggest that these oligomers could be a powerful new biomarker for the early detection of AD.
authors.affiliation: Research and Development, Novartis Vaccines and Diagnostics, Emeryville, California, United States of America.
authors.forename: Carol Man
authors.initials: CM
authors.lastname: Gao
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Yam
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Erika
authors.initials: E
authors.lastname: Magdangal
authors.forename: Cleo
authors.initials: C
authors.lastname: Salisbury
authors.forename: David
authors.initials: D
authors.lastname: Peretz
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Zuckermann
authors.forename: Michael D
authors.initials: MD
authors.lastname: Connolly
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Fedynyshyn
authors.forename: Sophie
authors.initials: S
authors.lastname: Allauzen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D008956:Models, Chemical; D008968:Molecular Conformation; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D012680:Sensitivity and Specificity
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D000939:Epitopes; D010446:Peptide Fragments; D010455:Peptides; C078592:amyloid beta-protein (1-40)