Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta
Oikonomidi A, Lewczuk P, Kornhuber J, Smulders Y, Linnebank M, Semmler A, Popp J (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 139
Pages Range: 324-332
Journal Issue: 2
DOI: 10.1111/jnc.13766
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 APP?, soluble APP?, and amyloid ?1-42 (A?1-42), 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 A?1-42 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 sAPP? and sAPP? were associated with high SAH levels. The results suggest that disturbed homocysteine metabolism is related to increased CSF levels of sAPP forms and A?1-42, 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 A?1-42, 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.
Authors with CRIS profile
Piotr Lewczuk
Department of Psychiatry and Psychotherapy
Johannes Kornhuber
Lehrstuhl für Psychiatrie und Psychotherapie
Involved external institutions
Vrije Universiteit Amsterdam (VU) / University Amsterdam
Netherlands (NL)
Universitätsspital Zürich (USZ)
Switzerland (CH)
Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV)
Switzerland (CH)
Netherlands (NL)
Universitätsspital Zürich (USZ)
Switzerland (CH)
Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV)
Switzerland (CH)
How to cite
APA:
Oikonomidi, A., Lewczuk, P., Kornhuber, J., Smulders, Y., Linnebank, M., Semmler, A., & Popp, J. (2016). Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta. Journal of Neurochemistry, 139(2), 324-332. https://doi.org/10.1111/jnc.13766
MLA:
Oikonomidi, Aikaterini, et al. "Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta." Journal of Neurochemistry 139.2 (2016): 324-332.
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