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J Neurochem. 2016 Oct;139(2):324-332. doi: 10.1111/jnc.13766. Epub 2016 Sep 30.

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

Author information

1
Department of Psychiatry, Division of Old Age Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
2
Department of Psychiatry and Psychotherapy, University of Erlangen, Erlangen, Germany.
3
Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Bialystok, Poland.
4
Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
5
Institute  for  Cardiovascular  Research  ICaR-VU, VU  University  Medical  Centre,  Amsterdam,  The Netherlands.
6
Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
7
Department of Psychiatry, Division of Old Age Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland. julius.popp@chuv.ch.
8
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany. julius.popp@chuv.ch.

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:

Alzheimer's disease; biomarkers; cerebrospinal fluid; homocysteine metabolism; soluble amyloid precursor protein

PMID:
27507672
DOI:
10.1111/jnc.13766
[Indexed for MEDLINE]
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