BACKGROUND: Amyloid precursor protein (APP) and amyloid β (Aβ) peptides are intensely studied in neuroscience and their cerebrospinal fluid (CSF) measurements may be used to track the metabolic pathways of APP in vivo. Reduced CSF levels of Aβ and soluble APP (sAPP) fragments are reported in inflammatory diseases, including multiple sclerosis (MS); but in MS, the precise pathway of APP metabolism and whether it can be affected by disease-modifying treatments remains unclear. OBJECTIVE: To characterize the CSF biomarkers of APP degradation in MS, including the effects of disease-modifying therapy. METHODS: CSF samples from 87 MS patients (54 relapsing-remitting (RR) MS; 33 secondary progressive (SP) MS and 28 controls were analyzed for sAPP and Aβ peptides by immunoassays, plus a subset of samples was analyzed by immunoprecipitation and mass spectrometry (IP-MS). Patients treated with natalizumab or mitoxantrone were examined at baseline, and after 1-2 years of treatment. RESULTS: CSF sAPP and Aβ peptide levels were reduced in MS patients; but they increased again towards normal, after natalizumab treatment. A multivariate model of IP-MS-measured Aβ species separated the SPMS patients from controls, with RRMS patients having intermediate levels. CONCLUSIONS: We confirmed and extended our previous observations of altered CSF sAPP and Aβ peptide levels in MS patients. We found that natalizumab therapy may be able to counteract the altered APP metabolism in MS. The CSF Aβ isoform distribution was found to be distinct in SPMS patients, as compared to the controls.
BACKGROUND:Amyloid precursor protein (APP) and amyloid β (Aβ) peptides are intensely studied in neuroscience and their cerebrospinal fluid (CSF) measurements may be used to track the metabolic pathways of APP in vivo. Reduced CSF levels of Aβ and soluble APP (sAPP) fragments are reported in inflammatory diseases, including multiple sclerosis (MS); but in MS, the precise pathway of APP metabolism and whether it can be affected by disease-modifying treatments remains unclear. OBJECTIVE: To characterize the CSF biomarkers of APP degradation in MS, including the effects of disease-modifying therapy. METHODS: CSF samples from 87 MS patients (54 relapsing-remitting (RR) MS; 33 secondary progressive (SP) MS and 28 controls were analyzed for sAPP and Aβ peptides by immunoassays, plus a subset of samples was analyzed by immunoprecipitation and mass spectrometry (IP-MS). Patients treated with natalizumab or mitoxantrone were examined at baseline, and after 1-2 years of treatment. RESULTS: CSF sAPP and Aβ peptide levels were reduced in MS patients; but they increased again towards normal, after natalizumab treatment. A multivariate model of IP-MS-measured Aβ species separated the SPMS patients from controls, with RRMS patients having intermediate levels. CONCLUSIONS: We confirmed and extended our previous observations of altered CSF sAPP and Aβ peptide levels in MS patients. We found that natalizumab therapy may be able to counteract the altered APP metabolism in MS. The CSF Aβ isoform distribution was found to be distinct in SPMS patients, as compared to the controls.
Authors: Pashtun Shahim; Yelverton Tegner; Niklas Marklund; Kina Höglund; Erik Portelius; David L Brody; Kaj Blennow; Henrik Zetterberg Journal: Neurology Date: 2017-03-10 Impact factor: 9.910
Authors: Niklas Mattsson; Philip S Insel; Michael Donohue; Susan Landau; William J Jagust; Leslie M Shaw; John Q Trojanowski; Henrik Zetterberg; Kaj Blennow; Michael W Weiner Journal: Brain Date: 2014-12-24 Impact factor: 13.501
Authors: Anna M Pietroboni; Tiziana Carandini; Annalisa Colombi; Matteo Mercurio; Laura Ghezzi; Giovanni Giulietti; Marta Scarioni; Andrea Arighi; Chiara Fenoglio; Milena A De Riz; Giorgio G Fumagalli; Paola Basilico; Maria Serpente; Marco Bozzali; Elio Scarpini; Daniela Galimberti; Giorgio Marotta Journal: Eur J Nucl Med Mol Imaging Date: 2018-10-21 Impact factor: 9.236
Authors: Niklas Mattsson; Philip S Insel; Susan Landau; William Jagust; Michael Donohue; Leslie M Shaw; John Q Trojanowski; Henrik Zetterberg; Kaj Blennow; Michael Weiner Journal: Ann Clin Transl Neurol Date: 2014-07-19 Impact factor: 4.511
Authors: Nina Rostgaard; Peter Roos; Erik Portelius; Kaj Blennow; Henrik Zetterberg; Anja H Simonsen; Jørgen E Nielsen Journal: Neurology Date: 2017-12-13 Impact factor: 9.910
Authors: Jordi A Matías-Guiu; Celia Oreja-Guevara; María Nieves Cabrera-Martín; Teresa Moreno-Ramos; José Luis Carreras; Jorge Matías-Guiu Journal: Front Neurol Date: 2016-03-31 Impact factor: 4.003