1. Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia
- Author
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Montse Ysamat, Ángela Alonso, Monica Diez-Fairen, Miquel Aguilar, Ignacio Alvarez, Juan Pablo Tartari, Britta Brix, Maria Carcel, Philipp Arendt, Jose Manuel González, and Pau Pastor
- Subjects
Pathology ,medicine.medical_specialty ,Amyloid ,tau Proteins ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Alzheimer Disease ,mental disorders ,medicine ,Amyloid precursor protein ,Humans ,Dementia ,Cognitive Dysfunction ,030212 general & internal medicine ,Cognitive decline ,Amyloid beta-Peptides ,biology ,business.industry ,Dementia with Lewy bodies ,medicine.disease ,Peptide Fragments ,Neurology ,Frontotemporal Dementia ,Positron-Emission Tomography ,biology.protein ,Neurology (clinical) ,Alzheimer's disease ,business ,Biomarkers ,030217 neurology & neurosurgery ,Frontotemporal dementia - Abstract
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, Aβ40 , Aβ38 , beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1), neurogranin (ng), phosphorylated neurofilament heavy-chain, and α-synuclein (α-syn) CSF levels were analyzed in 319 subjects, among whom 57 also underwent an amyloid PET scan. We also analyzed longitudinal clinical data from 239 subjects. 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.
- Published
- 2020
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