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Identification of n...
Identification of novel APP/Abeta isoforms in human cerebrospinal fluid.
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- Portelius, Erik, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Brinkmalm, Gunnar (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Tran, Ai Jun (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Brinkmalm-Westman, Ann, 1966 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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(creator_code:org_t)
- 2009-02-20
- 2009
- English.
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In: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 6:3, s. 87-94
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Abstract
Subject headings
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- BACKGROUND: Aggregation of beta-amyloid (Abeta) into oligomers and plaques is the central pathogenic mechanism in Alzheimer's disease (AD). Abeta is produced from the amyloid precursor protein (APP) by beta- and gamma-secretases, whereas, in the nonamyloidogenic pathway, alpha-secretase cleaves within the Abeta sequence, and thus precludes Abeta formation. A lot of research has focused on Abeta production and the neurotoxic 42-amino-acid form of Abeta (Abeta1-42), while less is known about the nonamyloidogenic pathway and how Abeta is degraded. OBJECTIVE: To study the Abeta metabolism in man by searching for novel Abeta peptides in cerebrospinal fluid (CSF). METHODS: Immunoprecipitation, using an anti-Abeta antibody, 6E10, was combined with either matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or nanoflow liquid chromatography and tandem mass spectrometry. RESULTS: We identified 12 truncated APP/Abeta peptides in the CSF, all of which end at amino acid 15 in the Abeta sequence, i.e. 1 amino acid before the proposed alpha-secretase site. Of these 12 APP/Abeta peptides, 11 are novel peptides and start N-terminally of the beta-secretase site. The most abundant APP/Abeta peptide starts 25 amino acids before the beta-secretase site, APP/Abeta (-25 to 15), and had a concentration of approximately 80 pg/ml. The identity of all the APP/Abeta peptides was verified in a cohort of AD patients and controls. A first pilot study also showed that the intensity of several APP/Abeta peaks in CSF was higher in AD cases than in controls. CONCLUSION: These data suggest an enzymatic activity that cleaves the precursor protein in a specific manner that may reflect a novel metabolic pathway for APP and Abeta.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
Keyword
- Aged
- Aged
- 80 and over
- Alzheimer Disease
- cerebrospinal fluid
- Amino Acid Sequence
- Amyloid Precursor Protein Secretases
- metabolism
- Amyloid beta-Protein
- cerebrospinal fluid
- metabolism
- Amyloid beta-Protein Precursor
- cerebrospinal fluid
- metabolism
- Chromatography
- Liquid
- Female
- Humans
- Immunoprecipitation
- Male
- Molecular Sequence Data
- Pilot Projects
- Spectrometry
- Mass
- Matrix-Assisted Laser Desorption-Ionization
Publication and Content Type
- ref (subject category)
- art (subject category)
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