Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia.
APOE
Alzheimer disease
amyloid
cerebrospinal fluid
positron emission tomography
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
07
11
2020
accepted:
16
11
2020
pubmed:
26
11
2020
medline:
13
8
2021
entrez:
25
11
2020
Statut:
ppublish
Résumé
Recently, some emerging cerebrospinal fluid (CSF) markers have been proposed as diagnostic tools for Alzheimer disease (AD) that can have an effect on disease progression. We analyze the accuracy of these CSF markers for diagnosis of AD in reference to brain amyloid positron emission tomography (PET). We also investigated whether they help in differentiating AD from other dementias and examined their influence in tracing the progression to dementia. Amyloid-β (Aβ) 1-42, total tau (t-tau), phosphorylated tau, Aβ Emerging CSF markers, especially ng/BACE-1 ratio (area under the curve = 0.77) and their combinations with core AD CSF markers (all AUCs >0.85), showed high accuracy to discriminate amyloid PET positivity. Subjects with AD had higher CSF BACE-1, ng, and α-syn levels than those with non-AD dementia. CSF t-tau/α-syn ratio was higher in subjects with dementia with Lewy bodies than in those with frontotemporal dementia. Most emerging/core AD ratios predicted a faster conversion from mild cognitive impairment (MCI) stage to AD and appeared to be helpful when core AD CSF markers were discordant. In addition, the rate of cognitive decline was associated with all CSF core AD markers, several emerging/core AD two-marker ratios, and CSF ng levels. These results suggest that emerging biomarkers in conjunction with core AD markers improve diagnosis of AD, are associated with the conversion from MCI into AD, and predict a faster progression of dementia.
Sections du résumé
BACKGROUND AND PURPOSE
Recently, some emerging cerebrospinal fluid (CSF) markers have been proposed as diagnostic tools for Alzheimer disease (AD) that can have an effect on disease progression. We analyze the accuracy of these CSF markers for diagnosis of AD in reference to brain amyloid positron emission tomography (PET). We also investigated whether they help in differentiating AD from other dementias and examined their influence in tracing the progression to dementia.
METHODS
Amyloid-β (Aβ) 1-42, total tau (t-tau), phosphorylated tau, Aβ
RESULTS
Emerging CSF markers, especially ng/BACE-1 ratio (area under the curve = 0.77) and their combinations with core AD CSF markers (all AUCs >0.85), showed high accuracy to discriminate amyloid PET positivity. Subjects with AD had higher CSF BACE-1, ng, and α-syn levels than those with non-AD dementia. CSF t-tau/α-syn ratio was higher in subjects with dementia with Lewy bodies than in those with frontotemporal dementia. Most emerging/core AD ratios predicted a faster conversion from mild cognitive impairment (MCI) stage to AD and appeared to be helpful when core AD CSF markers were discordant. In addition, the rate of cognitive decline was associated with all CSF core AD markers, several emerging/core AD two-marker ratios, and CSF ng levels.
CONCLUSIONS
These results suggest that emerging biomarkers in conjunction with core AD markers improve diagnosis of AD, are associated with the conversion from MCI into AD, and predict a faster progression of dementia.
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Peptide Fragments
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1142-1152Subventions
Organisme : NIH HHS
ID : K24HL148521
Pays : United States
Organisme : NIH HHS
ID : P30AG066511
Pays : United States
Informations de copyright
© 2020 European Academy of Neurology.
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