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Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection

Journal article
Authors Erika Ahlgren
Lars Hagberg
Dietmar Fuchs
Lars-Magnus Andersson
Staffan Nilsson
Henrik Zetterberg
Magnus Gisslén
Published in PLoS ONE
Volume 11
Issue 7
Pages e0158973
ISSN 1932-6203
Publication year 2016
Published at Department of Mathematical Sciences, Mathematical Statistics
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Biomedicine, Department of Infectious Medicine
Pages e0158973
Language en
Subject categories Neurochemistry


Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.

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