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Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease

BACKGROUND: Alzheimer's disease (AD) is associated with deposition of amyloid β (Aβ) in the brain, which is reflected by low concentration of the Aβ1-42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional Aβ peptides in human CSF and their relative abundance pattern is th...

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Autores principales: Portelius, Erik, Andreasson, Ulf, Ringman, John M, Buerger, Katharina, Daborg, Jonny, Buchhave, Peder, Hansson, Oskar, Harmsen, Andreas, Gustavsson, Mikael K, Hanse, Eric, Galasko, Douglas, Hampel, Harald, Blennow, Kaj, Zetterberg, Henrik
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818651/
https://www.ncbi.nlm.nih.gov/pubmed/20145736
http://dx.doi.org/10.1186/1750-1326-5-2
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author Portelius, Erik
Andreasson, Ulf
Ringman, John M
Buerger, Katharina
Daborg, Jonny
Buchhave, Peder
Hansson, Oskar
Harmsen, Andreas
Gustavsson, Mikael K
Hanse, Eric
Galasko, Douglas
Hampel, Harald
Blennow, Kaj
Zetterberg, Henrik
author_facet Portelius, Erik
Andreasson, Ulf
Ringman, John M
Buerger, Katharina
Daborg, Jonny
Buchhave, Peder
Hansson, Oskar
Harmsen, Andreas
Gustavsson, Mikael K
Hanse, Eric
Galasko, Douglas
Hampel, Harald
Blennow, Kaj
Zetterberg, Henrik
author_sort Portelius, Erik
collection PubMed
description BACKGROUND: Alzheimer's disease (AD) is associated with deposition of amyloid β (Aβ) in the brain, which is reflected by low concentration of the Aβ1-42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional Aβ peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of Aβ. Here, we test the hypothesis that AD is characterized by a specific CSF Aβ isoform pattern that is distinct when comparing sporadic AD (SAD) and familial AD (FAD) due to different mechanisms underlying brain amyloid pathology in the two disease groups. RESULTS: We measured Aβ isoform concentrations in CSF from 18 patients with SAD, 7 carriers of the FAD-associated presenilin 1 (PSEN1) A431E mutation, 17 healthy controls and 6 patients with depression using immunoprecipitation-mass spectrometry. Low CSF levels of Aβ1-42 and high levels of Aβ1-16 distinguished SAD patients and FAD mutation carriers from healthy controls and depressed patients. SAD and FAD were characterized by similar changes in Aβ1-42 and Aβ1-16, but FAD mutation carriers exhibited very low levels of Aβ1-37, Aβ1-38 and Aβ1-39. CONCLUSION: SAD patients and PSEN1 A431E mutation carriers are characterized by aberrant CSF Aβ isoform patterns that hold clinically relevant diagnostic information. PSEN1 A431E mutation carriers exhibit low levels of Aβ1-37, Aβ1-38 and Aβ1-39; fragments that are normally produced by γ-secretase, suggesting that the PSEN1 A431E mutation modulates γ-secretase cleavage site preference in a disease-promoting manner.
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spelling pubmed-28186512010-02-10 Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease Portelius, Erik Andreasson, Ulf Ringman, John M Buerger, Katharina Daborg, Jonny Buchhave, Peder Hansson, Oskar Harmsen, Andreas Gustavsson, Mikael K Hanse, Eric Galasko, Douglas Hampel, Harald Blennow, Kaj Zetterberg, Henrik Mol Neurodegener Research Article BACKGROUND: Alzheimer's disease (AD) is associated with deposition of amyloid β (Aβ) in the brain, which is reflected by low concentration of the Aβ1-42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional Aβ peptides in human CSF and their relative abundance pattern is thought to reflect the production and degradation of Aβ. Here, we test the hypothesis that AD is characterized by a specific CSF Aβ isoform pattern that is distinct when comparing sporadic AD (SAD) and familial AD (FAD) due to different mechanisms underlying brain amyloid pathology in the two disease groups. RESULTS: We measured Aβ isoform concentrations in CSF from 18 patients with SAD, 7 carriers of the FAD-associated presenilin 1 (PSEN1) A431E mutation, 17 healthy controls and 6 patients with depression using immunoprecipitation-mass spectrometry. Low CSF levels of Aβ1-42 and high levels of Aβ1-16 distinguished SAD patients and FAD mutation carriers from healthy controls and depressed patients. SAD and FAD were characterized by similar changes in Aβ1-42 and Aβ1-16, but FAD mutation carriers exhibited very low levels of Aβ1-37, Aβ1-38 and Aβ1-39. CONCLUSION: SAD patients and PSEN1 A431E mutation carriers are characterized by aberrant CSF Aβ isoform patterns that hold clinically relevant diagnostic information. PSEN1 A431E mutation carriers exhibit low levels of Aβ1-37, Aβ1-38 and Aβ1-39; fragments that are normally produced by γ-secretase, suggesting that the PSEN1 A431E mutation modulates γ-secretase cleavage site preference in a disease-promoting manner. BioMed Central 2010-01-14 /pmc/articles/PMC2818651/ /pubmed/20145736 http://dx.doi.org/10.1186/1750-1326-5-2 Text en Copyright ©2010 Portelius et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Portelius, Erik
Andreasson, Ulf
Ringman, John M
Buerger, Katharina
Daborg, Jonny
Buchhave, Peder
Hansson, Oskar
Harmsen, Andreas
Gustavsson, Mikael K
Hanse, Eric
Galasko, Douglas
Hampel, Harald
Blennow, Kaj
Zetterberg, Henrik
Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease
title Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease
title_full Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease
title_fullStr Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease
title_full_unstemmed Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease
title_short Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease
title_sort distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and psen1 a431e-associated familial alzheimer's disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818651/
https://www.ncbi.nlm.nih.gov/pubmed/20145736
http://dx.doi.org/10.1186/1750-1326-5-2
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