The cerebrospinal fluid biomarker ratio Aβ42/40 identifies amyloid positron emission tomography positivity better than Aβ42 alone in a heterogeneous memory clinic cohort.
Alzheimer’s Disease
Aβ42/40 Ratio
Biomarkers
Cerebrospinal Fluid
Positron Emission Tomography
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
26 04 2022
26 04 2022
Historique:
received:
17
11
2021
accepted:
08
04
2022
entrez:
27
4
2022
pubmed:
28
4
2022
medline:
29
4
2022
Statut:
epublish
Résumé
Cerebrospinal fluid (CSF) analysis for detecting amyloid positivity may be as reliable as positron emission tomography (PET). We evaluated the performance of the amyloid beta (Aβ)42/40 ratio for predicting amyloid positivity by PET, compared with Aβ42 alone, and phosphorylated tau 181 (pTau181)/Aβ42 and total tau (tTau)/Aβ42 ratios, using fully automated CSF immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) in a heterogeneous cohort of patients with a range of cognitive disorders reflecting the typical population of a memory clinic. CSF samples from 103 patients with known amyloid PET status (PET positive = 54; PET negative = 49) were retrospectively selected from one site in Germany; 71 patients were undergoing treatment for mild cognitive impairment (n = 44) or mild-to-moderate dementia (n = 27) due to Alzheimer's disease (AD), and 32 patients were undergoing treatment for non-AD-related cognitive disorders. Aβ42, pTau181, and tTau concentrations were measured in CSF samples using the respective Elecsys Point estimates for sensitivity and specificity of CSF biomarkers and biomarker ratios versus amyloid PET were 0.93 and 0.57 for Aβ42, 0.96 and 0.69 for pTau181/Aβ42, 0.92 and 0.69 for tTau/Aβ42, and 0.94 and 0.82 for Aβ42/40. For AUCs, point estimates (95% confidence intervals) versus amyloid PET were 0.78 (0.68-0.88) for Aβ42, 0.88 (0.81-0.95) for pTau181/Aβ42, 0.87 (0.80-0.95) for tTau/Aβ42, and 0.90 (0.83-0.97) for Aβ42/40. CSF Aβ42/40 ratio can predict PET amyloid positivity with high accuracy in patients with a range of cognitive disorders when evaluating Aβ pathology independent of tau and neurodegeneration for research purposes. The performance of Aβ42/40 was comparable with pTau181/Aβ42 and tTau/Aβ42 used in clinical practice and better than Aβ42 alone.
Sections du résumé
BACKGROUND
Cerebrospinal fluid (CSF) analysis for detecting amyloid positivity may be as reliable as positron emission tomography (PET). We evaluated the performance of the amyloid beta (Aβ)42/40 ratio for predicting amyloid positivity by PET, compared with Aβ42 alone, and phosphorylated tau 181 (pTau181)/Aβ42 and total tau (tTau)/Aβ42 ratios, using fully automated CSF immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) in a heterogeneous cohort of patients with a range of cognitive disorders reflecting the typical population of a memory clinic.
METHODS
CSF samples from 103 patients with known amyloid PET status (PET positive = 54; PET negative = 49) were retrospectively selected from one site in Germany; 71 patients were undergoing treatment for mild cognitive impairment (n = 44) or mild-to-moderate dementia (n = 27) due to Alzheimer's disease (AD), and 32 patients were undergoing treatment for non-AD-related cognitive disorders. Aβ42, pTau181, and tTau concentrations were measured in CSF samples using the respective Elecsys
RESULTS
Point estimates for sensitivity and specificity of CSF biomarkers and biomarker ratios versus amyloid PET were 0.93 and 0.57 for Aβ42, 0.96 and 0.69 for pTau181/Aβ42, 0.92 and 0.69 for tTau/Aβ42, and 0.94 and 0.82 for Aβ42/40. For AUCs, point estimates (95% confidence intervals) versus amyloid PET were 0.78 (0.68-0.88) for Aβ42, 0.88 (0.81-0.95) for pTau181/Aβ42, 0.87 (0.80-0.95) for tTau/Aβ42, and 0.90 (0.83-0.97) for Aβ42/40.
CONCLUSIONS
CSF Aβ42/40 ratio can predict PET amyloid positivity with high accuracy in patients with a range of cognitive disorders when evaluating Aβ pathology independent of tau and neurodegeneration for research purposes. The performance of Aβ42/40 was comparable with pTau181/Aβ42 and tTau/Aβ42 used in clinical practice and better than Aβ42 alone.
Identifiants
pubmed: 35473631
doi: 10.1186/s13195-022-01003-w
pii: 10.1186/s13195-022-01003-w
pmc: PMC9044878
doi:
Substances chimiques
Amyloid
0
Amyloid beta-Peptides
0
Biomarkers
0
Peptide Fragments
0
amyloid beta-protein (1-42)
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
60Informations de copyright
© 2022. The Author(s).
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