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

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.

• Authors: Aikaterini Oikonomidi, Piotr Lewczuk, Johannes Kornhuber, Yvo Smulders, Michael Linnebank, Alexander Semmler, Julius Popp
• Journal: Journal of neurochemistry (J Neurochem) Vol. 139 Issue 2 Pg. 324-332 (10 2016) ISSN: 1471-4159 [Electronic] England
• PMID: 27507672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 International Society for Neurochemistry.

Chemical References

• Albumins
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Apolipoprotein E4
• Peptide Fragments
• Tetrahydrofolates
• amyloid beta-protein (1-42)
• Homocysteine
• S-Adenosylmethionine
• Folic Acid
• Vitamin B 12
• 5-methyltetrahydrofolate

Topics

• Adult
• Albumins (metabolism)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Amyloid beta-Protein Precursor (cerebrospinal fluid)
• Apolipoprotein E4 (genetics)
• Female
• Folic Acid (cerebrospinal fluid)
• Healthy Volunteers
• Homocysteine (blood, cerebrospinal fluid, metabolism)
• Humans
• Male
• Middle Aged
• Neuropsychological Tests
• Peptide Fragments (cerebrospinal fluid)
• Reference Values
• S-Adenosylmethionine (cerebrospinal fluid)
• Tetrahydrofolates (cerebrospinal fluid)
• Vitamin B 12 (cerebrospinal fluid)