Harald Hampel1, Nicola Toschi2, Filippo Baldacci3, Henrik Zetterberg4, Kaj Blennow5, Ingo Kilimann6, Stefan J Teipel6, Enrica Cavedo7, Antonio Melo Dos Santos8, Stéphane Epelbaum8, Foudil Lamari9, Remy Genthon8, Bruno Dubois8, Roberto Floris10, Francesco Garaci11, Simone Lista1. 1. AXA Research Fund & Sorbonne Université Chair, Paris, France; Sorbonne Université, AP-HP, GRC n° 21, Alzheimer Precision Medicine (APM), Hôpital de la Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle Épinière (ICM), INSERM U 1127, CNRS UMR 7225, Paris, France; Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Paris, France. 2. Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy; Department of Radiology, "Athinoula A. Martinos" Center for Biomedical Imaging, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. 3. AXA Research Fund & Sorbonne Université Chair, Paris, France; Sorbonne Université, AP-HP, GRC n° 21, Alzheimer Precision Medicine (APM), Hôpital de la Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle Épinière (ICM), INSERM U 1127, CNRS UMR 7225, Paris, France; Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 4. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute, London, UK. 5. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 6. Department of Psychosomatic Medicine, University of Rostock & DZNE Rostock, Rostock, Germany. 7. AXA Research Fund & Sorbonne Université Chair, Paris, France; Sorbonne Université, AP-HP, GRC n° 21, Alzheimer Precision Medicine (APM), Hôpital de la Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle Épinière (ICM), INSERM U 1127, CNRS UMR 7225, Paris, France; Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Paris, France; IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. 8. Sorbonne Université, AP-HP, GRC n° 21, Alzheimer Precision Medicine (APM), Hôpital de la Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle Épinière (ICM), INSERM U 1127, CNRS UMR 7225, Paris, France; Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Paris, France. 9. AP-HP, UF Biochimie des Maladies Neuro-métaboliques, Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. 10. Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy. 11. Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy; Casa di Cura "San Raffaele Cassino", Cassino, Italy.
Abstract
INTRODUCTION: The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation. METHODS: The combinations ranking in the top 10 according to diagnostic accuracy in differentiating between distinct diagnostic categories were identified. RESULTS: The single biomarkers or biomarker combinations generating the best area under the receiver operating characteristics (AUROCs) were the following: the combination [amyloid β peptide + phosphorylated tau + neurofilament light chain] for distinguishing between ADD patients and HC (AUROC = 0.86), t-tau for distinguishing between ADD and FTD patients (AUROC = 0.82), and t-tau for distinguishing between FTD patients and HC (AUROC = 0.78). CONCLUSIONS: Novel and established cerebrospinal fluid markers perform with at least fair accuracy in the discrimination between ADD and FTD. The classification of mild cognitive impairment individuals was poor.
INTRODUCTION: The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation. METHODS: The combinations ranking in the top 10 according to diagnostic accuracy in differentiating between distinct diagnostic categories were identified. RESULTS: The single biomarkers or biomarker combinations generating the best area under the receiver operating characteristics (AUROCs) were the following: the combination [amyloid β peptide + phosphorylated tau + neurofilament light chain] for distinguishing between ADD patients and HC (AUROC = 0.86), t-tau for distinguishing between ADD and FTDpatients (AUROC = 0.82), and t-tau for distinguishing between FTDpatients and HC (AUROC = 0.78). CONCLUSIONS: Novel and established cerebrospinal fluid markers perform with at least fair accuracy in the discrimination between ADD and FTD. The classification of mild cognitive impairment individuals was poor.
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Authors: Sarinnapha M Vasunilashorn; Simon T Dillon; Noel Y Chan; Tamara G Fong; Marie Joseph; Bridget Tripp; Zhongcong Xie; Long H Ngo; Chun Geun Lee; Jack A Elias; Hasan H Otu; Sharon K Inouye; Edward R Marcantonio; Towia A Libermann Journal: J Gerontol A Biol Sci Med Sci Date: 2022-03-03 Impact factor: 6.053
Authors: Sarinnapha M Vasunilashorn; Simon T Dillon; Noel Y Chan; Tamara G Fong; Marie Joseph; Bridget Tripp; Zhongcong Xie; Long H Ngo; Chun Geun Lee; Jack A Elias; Hasan H Otu; Sharon K Inouye; Edward R Marcantonio; Towia A Libermann Journal: J Gerontol A Biol Sci Med Sci Date: 2022-03-03 Impact factor: 6.053
Authors: Katheryn A Q Cousins; David J Irwin; David A Wolk; Edward B Lee; Leslie M J Shaw; John Q Trojanowski; Fulvio Da Re; Garrett S Gibbons; Murray Grossman; Jeffrey S Phillips Journal: Brain Date: 2020-07-01 Impact factor: 13.501