title: Additional use of Aβ₄₂/Aβ₄₀ ratio with cerebrospinal fluid biomarkers P-tau and Aβ₄₂ increases the level of evidence of Alzheimer's disease pathophysiological process in routine practice.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) biomarkers have recently been included in the criteria for the diagnosis of Alzheimer's disease (AD). Since interpretation of CSF profile requires the combination of three parameters, biological data are not always conclusive and isolated elevation of phosphorylated tau (P-tau) or reduction of amyloid-β (Aβ)42 alone can be observed. In these cases, Aβ42/Aβ40 ratio could be more relevant than Aβ42 absolute values by considering inter-individual variations in the total amyloid load.
  
  
  OBJECTIVE
  The objective of this study was to assess the use of Aβ42/Aβ40 ratio to improve the accuracy of biological conclusions in the diagnosis of patients with ambiguous CSF Aβ42 or tau results.
  
  
  METHODS
  Among 386 lumbar punctures analyzed in the lab in 2 years, 122 showed ambiguous biological data that were completed by CSF Aβ40 quantification and Aβ42/Aβ40 ratio calculation. A biological conclusion was then made using 0.05 as the Aβ42/Aβ40 ratio cut-off.
  
  
  RESULTS
  Our results showed that one-third of the biological profiles of patients with atypical dementia were ambiguous. The addition of Aβ42/Aβ40 ratio increased the proportion of interpretable biological profiles from 69% to 87%, without changing the conclusion when usual biomarkers (Aβ42 and P-tau) were concordant.
  
  
  CONCLUSIONS
  Our results support the use of the Aβ42/Aβ40 ratio in addition to the usual CSF AD biomarkers for patients with ambiguous biological profiles. This method could be specifically directed to this population in order to improve the level of certainty for clinical routine practice.
authors.affiliation: Service de Neurologie, Centre Hospitalier Universitaire, Nancy, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Sauvée
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie - Endocrinologie - Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France.
authors.forename: Guerric
authors.initials: G
authors.lastname: DidierLaurent
authors.affiliation: INSERM, CIC-EC, CIE6, Université de Lorraine, Nancy, France Epidémiologie et Evaluation Cliniques, Centre Hospitalier Universitaire, Nancy, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Latarche
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie - Endocrinologie - Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Escanyé
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie - Endocrinologie - Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France UR AFPA - USC 340, Equipe BFLA, Université de Lorraine, Nancy, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Olivier
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie - Endocrinologie - Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France UR AFPA - USC 340, Equipe BFLA, Université de Lorraine, Nancy, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Malaplate-Armand
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003704:Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D013129:Spinal Puncture; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: A$\rmbeta$\(_{\rm{40}}\) peptide; A$\rmbeta$\(_{\rm{40}}\)/A$\rmbeta$\(_{\rm{42}}\) ratio; A$\rmbeta$\(_{\rm{42}}\) peptide; Alzheimer's disease; P-tau; cerebrospinal fluid; diagnosis; differential diagnosis