A single-nucleotide polymorphism of the osteopontin gene may contribute to a susceptibility to Lewy body disease

Maetzler, Walter; Michelis, Joan Philipp; Tomiuk, Juergen; Melms, Arthur; Becker, Clemens; Gasser, Thomas; Schulte, Claudia; Berg, Daniela

doi:10.1007/s00702-009-0209-x

Cited by 13 publications

(14 citation statements)

References 35 publications

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“…Their results showed that OPN was elevated in the CSF of familial AD mutation carriers compared to related noncarriers, which suggest changes of OPN in the CSF occurring a decade before clinical dementia. In addition, increased serum and CSF OPN levels were also detected in the Lewy dementia, and the genotypic variation of SNP-66 was associated with the occurrence of the Lewy body dementia [44]. These findings suggest that OPN is associated with the occurrence of cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

Elevated Osteopontin Levels in Mild Cognitive Impairment and Alzheimer’s Disease

Sun¹,

Yin

Guo

et al. 2013

Mediators of Inflammation

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Inflammatory mediators are closely associated with the pathogenesis of neurodegenerative changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Osteopontin (OPN) is a proinflammatory cytokine that has been shown to play an important role in various neuroinflammatory diseases. However, the function of OPN in AD and MCI progression is not well defined. Cerebrospinal fluid (CSF) and plasma samples were obtained from 35 AD patients, 31 MCI patients, and 20 other noninflammatory neurologic diseases (OND). Concentrations of OPN in the CSF and plasma were determined by enzyme-linked immunosorbent assay. During a 3-year clinical followup, 13 MCI patients converted to AD (MCI converters), and 18 were clinically stable (MCI nonconverters). CSF OPN concentrations were significantly increased in AD and MCI converters compared to OND, and increased levels of OPN in AD were associated with MMSE score; OPN protein levels both in the CSF and plasma of newly diagnosed AD patients were higher than that of chronical patients. In MCI converters individuals tested longitudinally, both plasma and CSF OPN concentrations were significantly elevated when they received a diagnosis of AD during followup. Further wide-scale studies are necessary to confirm these results and to shed light on the etiopathogenic role of osteopontin in AD.

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Section: Discussionmentioning

confidence: 99%

Elevated Osteopontin Levels in Mild Cognitive Impairment and Alzheimer’s Disease

Sun¹,

Yin

Guo

et al. 2013

Mediators of Inflammation

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“…The role of OPN in PD remains unknown but the reduction of OPN expression in nigral dopaminergic cells and the elevations in OPN levels found in CSF and plasma in PD suggest a significant contribution (Iczkiewicz et al. 2006; Maetzler et al. 2007, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…2006). OPN is present in Lewy bodies and there are higher levels of OPN in the CSF and serum of patients with Lewy body disease compared to control individuals (Maetzler et al. 2007, 2009).…”

mentioning

confidence: 99%

The RGD‐containing peptide fragment of osteopontin protects tyrosine hydroxylase positive cells against toxic insult in primary ventral mesencephalic cultures and in the rat substantia nigra

Iczkiewicz

Broom

Cooper

et al. 2010

Journal of Neurochemistry

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J. Neurochem. (2010) 114, 1792–1804. Abstract We have previously shown that the multi‐functional phosphoprotein osteopontin (OPN) is present in the substantia nigra (SN) and that its mRNA and protein expression are up‐regulated following toxic insult. We now report the effects of the arginine‐glycine‐aspartic acid (RGD)‐containing peptide fragment of OPN and OPN inactivation on the survival of tyrosine hydroxylase (TH) positive neurones in primary rat ventral mesencephalic (VM) cultures and in SN in the rat. Treatment of VM cultures with the fragment of OPN containing the RGD integrin binding domain did not decrease TH positive cell number, but instead the peptide fragment protected against cell loss induced by both MPP+ and lipopolysaccharide (LPS). Incorporation of an OPN antibody into VM cultures caused a concentration‐dependent loss of TH positive neurones. The OPN antibody also exacerbated MPP+‐ and LPS‐induced cell loss at all concentrations tested. In the rat, administration of the RGD‐containing peptide fragment of OPN protected TH positive neurones against a mechanically‐induced lesion and against 6‐hydroxydopamine‐ and LPS‐induced cell loss. The protection against 6‐hydroxydopamine toxicity was confirmed in a separate study using stereological analysis. By contrast, stereotaxic injection of the OPN antibody into the SN resulted in a loss of TH positive cells. These results suggest that OPN may be necessary for the survival of TH positive cells in SN but through the RGD‐containing peptide fragment may also have neuroprotective properties relevant to Parkinson’s disease.

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“…7 The manifold higher abundance of OPN in cerebrospinal fluid than in blood 8,9 argues for a crucial role of this protein in central nervous system (CNS) physiology and pathology. In the developing and adult (rodent) brain, neurons of the olfactory bulb, retina, striatum, and brainstem are OPN-positive.…”

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confidence: 99%

Progressive Secondary Neurodegeneration and Microcalcification Co-Occur in Osteopontin-Deficient Mice

Maetzler

Berg

Funke

et al. 2010

The American Journal of Pathology

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In the brain, osteopontin (OPN) may function in a variety of pathological conditions, including neurodegeneration, microcalcification, and inflammation. In this study, we addressed the role of OPN in primary and secondary neurodegeneration, microcalcification, and inflammation after an excitotoxic lesion by examining OPN knock-out (KO) mice. Two, four, and ten weeks after injection of the glutamate analogue ibotenate into the corticostriatal boundary, the brains of 12 mice per survival time and strain were evaluated. OPN was detectable in neuron-shaped cells, in microglia, and at the surface of dense calcium deposits. At this primary lesion site, although the glial reaction was attenuated in OPN-KO mice, lesion size and presence of microcalcification were comparable between OPN-KO and wild-type mice. In contrast, secondary neurodegeneration at the thalamus was more prominent in OPN-KO mice, and this difference increased over time. This was paralleled by a dramatic rise in the regional extent of dense microcalcification. Despite these differences, the numbers of glial cells did not significantly differ between the two strains. This study demonstrates for the first time a genetic model with co-occurrence of neurodegeneration and microcalcification, mediated by the lack of OPN, and suggests a basic involvement of OPN action in these conditions. In the case of secondary retrograde or transneuronal degeneration, OPN may have a protective role as intracellular actor.

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A single-nucleotide polymorphism of the osteopontin gene may contribute to a susceptibility to Lewy body disease

Cited by 13 publications

References 35 publications

Elevated Osteopontin Levels in Mild Cognitive Impairment and Alzheimer’s Disease

Elevated Osteopontin Levels in Mild Cognitive Impairment and Alzheimer’s Disease

The RGD‐containing peptide fragment of osteopontin protects tyrosine hydroxylase positive cells against toxic insult in primary ventral mesencephalic cultures and in the rat substantia nigra

Progressive Secondary Neurodegeneration and Microcalcification Co-Occur in Osteopontin-Deficient Mice

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