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01-06-2014 | Original Paper

Altered Cerebrospinal Fluid Levels of Amyloid β and Amyloid Precursor-Like Protein 1 Peptides in Down’s Syndrome

Authors: Erik Portelius, Mikko Hölttä, Hilkka Soininen, Maria Bjerke, Henrik Zetterberg, Anni Westerlund, Sanna-Kaisa Herukka, Kaj Blennow, Niklas Mattsson

Published in: NeuroMolecular Medicine | Issue 2/2014

Abstract

Down’s syndrome (DS) patients develop early Alzheimer’s disease pathology with abundant cortical amyloid plaques, likely due to overproduction of the amyloid precursor protein (APP), which subsequently leads to amyloid β (Aβ) aggregation. This is reflected in cerebrospinal fluid (CSF) levels of the 42-amino acid long Aβ peptide (Aβ1-42), which are increased in young DS patients and decreases with age. However, it is unclear whether DS also affects other aspects of Aβ metabolism, including production of shorter C- and N-terminal truncated Aβ peptides, and production of peptides from the amyloid precursor-like protein 1 (APLP1), which is related to APP, and cleaved by the same enzymatic processing machinery. APLP1-derived peptides may be surrogate markers for Aβ1-42 production in the brain. Here, we used hybrid immunoaffinity–mass spectrometry and enzyme-linked immunosorbent assays to monitor several Aβ and APLP1 peptides in CSF from DS patients (n = 12) and healthy controls (n = 20). CSF levels of Aβ1-42 and three endogenous peptides derived from APLP1 (APL1β25, APL1β27 and APL1β28) were decreased in DS compared with controls, while a specific Aβ peptide, Aβ1-28, was increased in a majority of the DS individuals. This study indicates that DS causes previously unknown specific alterations of APP and APLP1 metabolism.

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Title: Altered Cerebrospinal Fluid Levels of Amyloid β and Amyloid Precursor-Like Protein 1 Peptides in Down’s Syndrome
Authors: Erik Portelius
Mikko Hölttä
Hilkka Soininen
Maria Bjerke
Henrik Zetterberg
Anni Westerlund
Sanna-Kaisa Herukka
Kaj Blennow
Niklas Mattsson
Publication date: 01-06-2014
Publisher: Springer US
Published in: NeuroMolecular Medicine / Issue 2/2014
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-014-8302-1

At a glance: The STEP trials

Springer Medicine

Altered Cerebrospinal Fluid Levels of Amyloid β and Amyloid Precursor-Like Protein 1 Peptides in Down’s Syndrome

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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