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Cited by 253

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

Cerebrospinal Fluid Aβ 42/40 Corresponds Better than Aβ 42 to Amyloid PET in Alzheimer’s Disease

Lewczuk, Piotr, Matzen, Anja, Blennow, Kaj, Parnetti, Lucilla, Molinuevo, Jose Luis, Eusebi, Paolo, Kornhuber, Johannes, Morris, John C., Fagan, Anne M.·2016·Journal of Alzheimer’s Disease
DOI 10.3233/jad-160722PMC PMC5147502
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Abstract

Background: Decreased concentrations of amyloid-β 1-42 (Aβ 42 ) 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 Aβ 42/40 ratio seems to be a more accurate biomarker of clinical AD than CSF Aβ 42 alone. Objective: We tested whether CSF Aβ 42 alone or the Aβ 42/40 ratio corresponds better with amyloid PET status and analyzed the distribution of cases with discordant CSF-PET results. Methods: 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 Aβ 42 and Aβ 40 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. Results: CSF Aβ 42/40 corresponded better than Aβ 42 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. Conclusion: The CSF Aβ 42/40 ratio is superior to Aβ 42 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.

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Metadata

Authors
Lewczuk, P., Matzen, A., Blennow, K., Parnetti, L., Molinuevo, J. L., Eusebi, P., Kornhuber, J., Morris, J. C., & Fagan, A. M.
Affiliations
  • Universitätsklinikum Erlangen
  • IBL International GmbH, Hamburg, Germany
  • the Sahlgrenska Academy at the University of Gothenburg
  • University of Perugia
  • Hospital Clínic de Barcelona – Universitat de Barcelona
  • Washington University School of Medicine
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2016-10-14
Volume
55
Issue
2
Pages
813-822
ISSN
  • 1387-2877
  • 1875-8908
DOI
10.3233/jad-160722
PMC
PMC5147502
Cited by
253
References
12
Language
en
Licence

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