Activated MAO-B in the brain of alzheimer patients, demonstrated by [ 11C]-l-deprenyl using whole hemisphere autoradiography

Balázs Gulyás, Elena Pavlova, P. Kása, K. Gulya, Lidia Bakota, Szilvia Várszegi, E. Keller, Mónika Csilla Horváth, Sangram Nag, I. Hermecz, K. Magyar, Christer Halldin

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Abstract

In the human brain the monoaminooxidase-B enzyme or MAO-B is highly abundant in astrocytes. As astrocyte activity and, consequently, the activity of the MAO-B enzyme, is up-regulated in neuroinflammatory processes, radiolabelled analogues of deprenyl may serve as an imaging biomarker in neuroinflammation and neurodegeneration, including Alzheimer's disease. In the present study [11C]-l-deprenyl, the PET radioligand version of l-deprenyl or selegiline®, a selective irreversible MAO-B inhibitor was used in whole hemisphere autoradiographic experiments in human brain sections in order to test the radioligand's binding to the MAO-B enzyme in human brain tissue, with an eye on exploring the radioligand's applicability as a molecular imaging biomarker in human PET studies, with special regard to diagnostic detection of reactive astrogliosis. Whole hemisphere brain sections obtained from Alzheimer patients and from age matched control subjects were examined. In control brains the binding of [11C]-l-deprenyl was the highest in the hippocampus, in the basal ganglia, the thalamus, the substantia nigra, the corpus geniculatum laterale, the nucleus accumbens and the periventricular grey matter. In Alzheimer brains significantly higher binding was observed in the temporal lobes and the white matter. Furthermore, in the Alzheimer brains in the hippocampus, temporal lobe and white matter the binding negatively correlated with Braak stages. The highest binding was observed in Braak I-II, whereas it decreased with increasing Braak grades. The increased regional binding in Alzheimer brains coincided with the presence of an increased number of activated astrocytes, as demonstrated by correlative immunohistochemical studies with GFAP in adjacent brain slices. Deprenyl itself as well as the MAO-B antagonist rasagiline did effectively block the binding of the radioligand, whereas the MAO-A antagonist pirlindole did not affect it. Compounds with high affinity for the PBR system did not block the radioligand binding either, providing evidence for the specificity of [11C]-l-deprenyl for the MAO-B enzyme. In conclusion, the present observations indicate that [11C]-l-deprenyl may be a promising and selective imaging biomarker of increased MAO-B activity in the human brain and can therefore serve as a prospective PET tracer targeting neuroinflammation and neurodegeneration.

Original languageEnglish
Pages (from-to)60-68
Number of pages9
JournalNeurochemistry International
Volume58
Issue number1
DOIs
Publication statusPublished - Jan 2011

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Selegiline
Monoamine Oxidase
Autoradiography
Brain
Astrocytes
Biomarkers
Temporal Lobe
Enzymes
Hippocampus
Molecular Imaging
Monoamine Oxidase Inhibitors
Nucleus Accumbens
Substantia Nigra
Basal Ganglia
Thalamus
Human Activities
Alzheimer Disease

Keywords

  • [C]-l-Deprenyl
  • Alzheimer's disease
  • Astrocyte
  • Human brain
  • L-Deprenyl
  • MAO-B inhibitor
  • Selegiline
  • Whole hemisphere autoradiography

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Activated MAO-B in the brain of alzheimer patients, demonstrated by [ 11C]-l-deprenyl using whole hemisphere autoradiography. / Gulyás, Balázs; Pavlova, Elena; Kása, P.; Gulya, K.; Bakota, Lidia; Várszegi, Szilvia; Keller, E.; Horváth, Mónika Csilla; Nag, Sangram; Hermecz, I.; Magyar, K.; Halldin, Christer.

In: Neurochemistry International, Vol. 58, No. 1, 01.2011, p. 60-68.

Research output: Contribution to journalArticle

Gulyás, Balázs ; Pavlova, Elena ; Kása, P. ; Gulya, K. ; Bakota, Lidia ; Várszegi, Szilvia ; Keller, E. ; Horváth, Mónika Csilla ; Nag, Sangram ; Hermecz, I. ; Magyar, K. ; Halldin, Christer. / Activated MAO-B in the brain of alzheimer patients, demonstrated by [ 11C]-l-deprenyl using whole hemisphere autoradiography. In: Neurochemistry International. 2011 ; Vol. 58, No. 1. pp. 60-68.
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AU - Gulya, K.

AU - Bakota, Lidia

AU - Várszegi, Szilvia

AU - Keller, E.

AU - Horváth, Mónika Csilla

AU - Nag, Sangram

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AU - Magyar, K.

AU - Halldin, Christer

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