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NeuroMolecular Medicine

, Volume 16, Issue 2, pp 510–516 | Cite as

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

  • Erik Portelius
  • Mikko Hölttä
  • Hilkka Soininen
  • Maria Bjerke
  • Henrik Zetterberg
  • Anni Westerlund
  • Sanna-Kaisa Herukka
  • Kaj Blennow
  • Niklas Mattsson
Original Paper

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.

Keywords

Down’s syndrome Amyloid β Amyloid precursor-like protein 1 Mass spectrometry Cerebrospinal fluid 

Notes

Acknowledgments

The study was supported by the Swedish Research Council (Project Nos. 14002, K2010-63P-21562-01-4, K2011-61X-20401-05-6), Stiftelsen Gamla Tjänarinnor, Magn. Bergvalls Stiftelse, Gun och Bertil Stohnes Stiftelse, the Swedish Brain Fund, the Alzheimer Foundation, Sweden, the Dementia Association, Sweden, Wenner-gren foundation, Strategic for UEFBRAIN and the JPND Project BIOMARKAPD, Göteborgs Läkaresällskap, Svenska Läkaresällskapet, Klinisk Biokemi i Norden, Carl-Bertil Laurells fond.

Conflict of interest

All authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Erik Portelius
    • 1
  • Mikko Hölttä
    • 1
  • Hilkka Soininen
    • 2
    • 3
  • Maria Bjerke
    • 1
  • Henrik Zetterberg
    • 1
    • 4
  • Anni Westerlund
    • 1
  • Sanna-Kaisa Herukka
    • 2
    • 3
  • Kaj Blennow
    • 1
  • Niklas Mattsson
    • 1
    • 5
    • 6
  1. 1.Department of Psychiatry and Neurochemistry, Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at the University of GothenburgGothenburgSweden
  2. 2.Kuopio University HospitalKuopioFinland
  3. 3.School of Medicine, Institute of Clinical Medicine - NeurologyUniversity of Eastern FinlandKuopioFinland
  4. 4.Department of Molecular NeuroscienceUCL Institute of NeurologyLondonUK
  5. 5.San Francisco VA Medical Center, Center for Imaging of Neurodegenerative Diseases (CIND)University of California San FranciscoSan FranciscoUSA
  6. 6.Department of Radiology and Biomedical ImagingUniversity of CaliforniaSan FranciscoUSA

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