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Title

Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta

Authors
Oikonomidi, Aikaterini
Lewczuk, Piotr
Kornhuber, Johannes
Smulders, Yvo
Linnebank, Michael
Semmler, Alexander
Published in Journal of Neurochemistry. 2016, vol. 139, no. 2, p. 324-332
Abstract Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. The objective of this study was to investigate the relationships between cerebral amyloid production and both blood and cerebrospinal fluid (CSF) markers of the homocysteine metabolism. We assessed CSF concentrations of soluble APPα, soluble APPβ, and amyloid β1-42 (Aβ1-42), as well as plasma levels of homocysteine (Hcys), total vitamin B12, and folate, and CSF concentrations of homocysteine (Hcys-CSF), 5-methyltetrahydrofolate (5-MTHF), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) in 59 subjects with normal cognition. Linear regression analyses were performed to assess associations between homocysteine metabolism parameters and amyloid production. The study was approved by the Ethical Committee of the University of Bonn. After controlling for age, gender, APOEe4 status, and albumin ratio (Qalb), higher Aβ1-42 CSF levels were associated with high Hcys and low vitamin B12 plasma levels as well as with high Hcys, high SAH, and low 5-MTHF CSF levels. Higher CSF concentrations of sAPPα and sAPPβ were associated with high SAH levels. The results suggest that disturbed homocysteine metabolism is related to increased CSF levels of sAPP forms and Aβ1-42, and may contribute to the accumulation of amyloid pathology in the brain. Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. We found associations between CSF levels of soluble APP forms and Aβ1-42, and markers of the homocysteine metabolism in both plasma and CSF in adults with normal cognition. Disturbed homocysteine metabolism may represent a target for preventive and early disease-modifying interventions in Alzheimer's disease.
Keywords AdultAlbumins/metabolismAmyloid beta-Peptides/cerebrospinal fluidAmyloid beta-Protein Precursor/cerebrospinal fluidApolipoprotein E4/geneticsFemaleFolic Acid/cerebrospinal fluidHealthy VolunteersHomocysteine/blood/cerebrospinal fluid/metabolismHumansMaleMiddle AgedNeuropsychological TestsPeptide Fragments/cerebrospinal fluidReference ValuesS-Adenosylmethionine/cerebrospinal fluidTetrahydrofolates/cerebrospinal fluidVitamin B 12/cerebrospinal fluid
Identifiers
PMID: 27507672
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Article (Published version) (308 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Research group Neuropsychiatrie et Biomarqueurs de la maladie d'Alzheimer (991)
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OIKONOMIDI, Aikaterini et al. Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta. In: Journal of Neurochemistry, 2016, vol. 139, n° 2, p. 324-332. https://archive-ouverte.unige.ch/unige:105994

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Deposited on : 2018-06-28

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