Giulia Giacomucci1, Salvatore Mazzeo1,2, Silvia Bagnoli1, Matteo Casini3, Sonia Padiglioni1, Cristina Polito1,2, Valentina Berti4,5, Juri Balestrini1, Camilla Ferrari1, Gemma Lombardi2, Assunta Ingannato1, Sandro Sorbi1,2, Benedetta Nacmias1,2, Valentina Bessi1. 1. Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence (NEUROFARBA), Azienda Ospedaliera-Universitaria Careggi, Largo Brambilla 3, 50134 Florence, Italy. 2. IRCCS Fondazione Don Carlo Gnocchi, Via Scandicci 269, 50143 Florence, Italy. 3. Faculty of Medicine and Surgery, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. 4. Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Via Giovanni Battista Morgagni 50, 50134 Florence, Italy. 5. Nuclear Medicine Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Piero Palagi 1, 50139 Florence, Italy.
Abstract
BACKGROUND: The aims of this study were to compare the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of different cerebrospinal fluid (CSF) amyloid biomarkers and amyloid-Positron Emission Tomography (PET) in patients with a clinical diagnosis of Alzheimer's disease (AD) and Frontotemporal Dementia (FTD); to compare concordance between biomarkers; and to provide an indication of their use and interpretation. METHODS: We included 148 patients (95 AD and 53 FTD), who underwent clinical evaluation, neuropsychological assessment, and at least one amyloid biomarker (CSF analysis or amyloid-PET). Thirty-six patients underwent both analyses. One-hundred-thirteen patients underwent Apolipoprotein E (ApoE) genotyping. RESULTS: Amyloid-PET presented higher diagnostic accuracy, sensitivity, and NPV than CSF Aβ1-42 but not Aβ42/40 ratio. Concordance between CSF biomarkers and amyloid-PET was higher in FTD patients compared to AD cases. None of the AD patients presented both negative Aβ biomarkers. CONCLUSIONS: CSF Aβ42/40 ratio significantly increased the diagnostic accuracy of CSF biomarkers. On the basis of our current and previous data, we suggest a flowchart to guide the use of biomarkers according to clinical suspicion: due to the high PPV of both amyloid-PET and CSF analysis including Aβ42/40, in cases of concordance between at least one biomarker and clinical diagnosis, performance of the other analysis could be avoided. A combination of both biomarkers should be performed to better characterize unclear cases. If the two amyloid biomarkers are both negative, an underlying AD pathology can most probably be excluded.
BACKGROUND: The aims of this study were to compare the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of different cerebrospinal fluid (CSF) amyloid biomarkers and amyloid-Positron Emission Tomography (PET) in patients with a clinical diagnosis of Alzheimer's disease (AD) and Frontotemporal Dementia (FTD); to compare concordance between biomarkers; and to provide an indication of their use and interpretation. METHODS: We included 148 patients (95 AD and 53 FTD), who underwent clinical evaluation, neuropsychological assessment, and at least one amyloid biomarker (CSF analysis or amyloid-PET). Thirty-six patients underwent both analyses. One-hundred-thirteen patients underwent Apolipoprotein E (ApoE) genotyping. RESULTS: Amyloid-PET presented higher diagnostic accuracy, sensitivity, and NPV than CSF Aβ1-42 but not Aβ42/40 ratio. Concordance between CSF biomarkers and amyloid-PET was higher in FTDpatients compared to AD cases. None of the ADpatients presented both negative Aβ biomarkers. CONCLUSIONS: CSF Aβ42/40 ratio significantly increased the diagnostic accuracy of CSF biomarkers. On the basis of our current and previous data, we suggest a flowchart to guide the use of biomarkers according to clinical suspicion: due to the high PPV of both amyloid-PET and CSF analysis including Aβ42/40, in cases of concordance between at least one biomarker and clinical diagnosis, performance of the other analysis could be avoided. A combination of both biomarkers should be performed to better characterize unclear cases. If the two amyloid biomarkers are both negative, an underlying AD pathology can most probably be excluded.
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