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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.
J Alzheimers Dis. 2014; 41(2):377-86.JA

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.

CONCLUSION

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Sauvée M
Service de Neurologie, Centre Hospitalier Universitaire, Nancy, France.
DidierLaurent G
Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie - Endocrinologie - Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France.
Latarche C
INSERM, CIC-EC, CIE6, Université de Lorraine, Nancy, France Epidémiologie et Evaluation Cliniques, Centre Hospitalier Universitaire, Nancy, France.
Escanyé MC
Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie - Endocrinologie - Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France.
Olivier JL
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.
Malaplate-Armand C
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.

MeSH

AdultAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognitive DysfunctionDementiaDiagnosis, DifferentialFemaleHumansLewy Body DiseaseMaleMiddle AgedPeptide FragmentsPhosphorylationSpinal PunctureYoung Adulttau Proteins

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

24614902

Citation

Sauvée, Mathilde, et al. "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." Journal of Alzheimer's Disease : JAD, vol. 41, no. 2, 2014, pp. 377-86.
Sauvée M, DidierLaurent G, Latarche C, et al. 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. J Alzheimers Dis. 2014;41(2):377-86.
Sauvée, M., DidierLaurent, G., Latarche, C., Escanyé, M. C., Olivier, J. L., & Malaplate-Armand, C. (2014). 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. Journal of Alzheimer's Disease : JAD, 41(2), 377-86. https://doi.org/10.3233/JAD-131838
Sauvée M, et al. 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. J Alzheimers Dis. 2014;41(2):377-86. PubMed PMID: 24614902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Sauvée,Mathilde, AU - DidierLaurent,Guerric, AU - Latarche,Clotilde, AU - Escanyé,Marie-Christine, AU - Olivier,Jean-Luc, AU - Malaplate-Armand,Catherine, PY - 2014/3/12/entrez PY - 2014/3/13/pubmed PY - 2015/2/11/medline KW - A$\rmbeta$\(_{\rm{40}}\) peptide KW - A$\rmbeta$\(_{\rm{40}}\)/A$\rmbeta$\(_{\rm{42}}\) ratio KW - A$\rmbeta$\(_{\rm{42}}\) peptide KW - Alzheimer's disease KW - P-tau KW - cerebrospinal fluid KW - diagnosis KW - differential diagnosis SP - 377 EP - 86 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 41 IS - 2 N2 - 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. CONCLUSION: 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/24614902/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_ DB - PRIME DP - Unbound Medicine ER -