title: Cerebrospinal Fluid Aβ42/40 Corresponds Better than Aβ42 to Amyloid PET in Alzheimer's Disease.
abstract: Decreased concentrations of amyloid-β 1-42 (Aβ42) in cerebrospinal fluid (CSF) and increased retention of Aβ tracers in the brain on positron emission tomography (PET) are considered the earliest biomarkers of Alzheimer's disease (AD). However, a proportion of cases show discrepancies between the results of the two biomarker modalities which may reflect inter-individual differences in Aβ metabolism. The CSF Aβ42/40 ratio seems to be a more accurate biomarker of clinical AD than CSF Aβ42 alone.
  
  
  
  We tested whether CSF Aβ42 alone or the Aβ42/40 ratio corresponds better with amyloid PET status and analyzed the distribution of cases with discordant CSF-PET results.
  
  
  
  CSF obtained from a mixed cohort (n = 200) of cognitively normal and abnormal research participants who had undergone amyloid PET within 12 months (n = 150 PET-negative, n = 50 PET-positive according to a previously published cut-off) was assayed for Aβ42 and Aβ40 using two recently developed immunoassays. Optimal CSF cut-offs for amyloid positivity were calculated, and concordance was tested by comparison of the areas under receiver operating characteristic (ROC) curves (AUC) and McNemar's test for paired proportions.
  
  
  
  CSF Aβ42/40 corresponded better than Aβ42 with PET results, with a larger proportion of concordant cases (89.4% versus 74.9%, respectively, p < 0.0001) and a larger AUC (0.936 versus 0.814, respectively, p < 0.0001) associated with the ratio. For both CSF biomarkers, the percentage of CSF-abnormal/PET-normal cases was larger than that of CSF-normal/PET-abnormal cases.
  
  
  
  The CSF Aβ42/40 ratio is superior to Aβ42 alone as a marker of amyloid-positivity by PET. We hypothesize that this increase in performance reflects the ratio compensating for general between-individual variations in CSF total Aβ.
authors: Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany.|Department of Neurodegeneration Diagnostics, Medical University of Białystok, and Department of Biochemical Diagnostics, University Hospital of Bialystok, Bialystok, Poland.
authors: Piotr
authors: P
authors: Lewczuk
authors: IBL International GmbH, Hamburg, Germany.
authors: Anja
authors: A
authors: Matzen
authors: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Kaj
authors: K
authors: Blennow
authors: Section of Neurology, Center for Memory Disturbances, University of Perugia, Italy.
authors: Lucilla
authors: L
authors: Parnetti
authors: Alzheimer's disease and other cognitive disorders unit, Neurology Service, Hospital Clínic de Barcelona - Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
authors: Jose Luis
authors: JL
authors: Molinuevo
authors: Section of Neurology, Center for Memory Disturbances, University of Perugia, Italy.
authors: Paolo
authors: P
authors: Eusebi
authors: Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany.
authors: Johannes
authors: J
authors: Kornhuber
authors: The Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors: John C
authors: JC
authors: Morris
authors: The Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Anne M
authors: AM
authors: Fagan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging* / Q000235:genetics; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000814:Aniline Compounds / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000378:metabolism
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; amyloid-β; biomarker; cerebrospinal fluid; positron emission tomography