Cystatin C expression in ischemic white matter lesions

Umegae, Nobuyuki; Nagai, Atsushi; Terashima, Masaharu; Watanabe, Terubumi; Shimode, Koichi; Kobayashi, Shotai; Masuda, Junichi; Kim, S. U.; Yamaguchi, Shûhei

doi:10.1111/j.1600-0404.2007.00984.x

Cited by 13 publications

(20 citation statements)

References 33 publications

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“…However, higher levels of serum cystatin C have also been associated with cognitive decline34 35 and with WML36 in large population-based cohort studies. In WML, the cystatin C expression is upregulated in astrocytes, presumably due to a self-defence response in the process of white matter degeneration37 Our results, based on EV -cystatin C, show similar results as increasing EV-cystatin C is related to increased volume of WML. Cystatin C is secreted by all human tissues38 which presumably concomitantly shed cystatin C + EVs in order to directly influence more distant processes.…”

Section: Discussionsupporting

confidence: 81%

Extracellular vesicle protein levels are related to brain atrophy and cerebral white matter lesions in patients with manifest vascular disease: the SMART-MR study

et al. 2014

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ObjectivesExtracellular vesicles (EVs) and their protein levels have been identified as a potential risk marker for the development of vascular disease. In the present study, we assessed whether levels of four previously identified EV proteins (cystatin C, serpin G1, serpin F2 and CD14) are associated with cerebral white matter lesions (WMLs) and brain atrophy.DesignCohort study; cross-sectional and prospective.SettingSingle centre, secondary and tertiary setting.Participants1309 patients with manifest vascular disease from the Second Manifestations of ARTerial disease-MR (SMART-MR) study, of which 994 had successful brain MRI and EV protein level measurements.OutcomesWML and brain parenchymal fraction (BPF), as parameter for brain atrophy, at baseline and follow-up.Statistical methodsThe relationship between EV protein levels and WML volume (expressed as log transformed percentage of intracranial volume) and BPF (expressed percentage of intracranial volume) on 1.5 T brain MRI was assessed with multivariable linear regression modelling. Subsequently, the relationship between baseline EV protein levels and progression of atrophy and WML was analysed in 534 patients, in whom a follow-up MRI was obtained after 4 years.ResultsHigher EV-cystatin C and EV-CD14 were significantly associated with larger WML volume (linear regression coefficient (95% CI) 0.10 log %/SD (0.04 to 0.17) and 0.14 log %/SD (0.07 to 0.20), respectively. Higher EV-CD14 was associated with more brain atrophy (–0.14%/SD; –0.27 to –0.01). Baseline EV-CD14 was significantly associated with increase of WMLs (0.11 log %/SD (0.04 to 0.18)). No relationship with EV-serpins was observed at baseline or at follow-up.ConclusionsEV proteins cystatin C and CD14 are related to cerebral WMLs and the progression of brain atrophy in patients with manifest vascular disease, potentially identifying EVs in the aetiology of structural brain changes.

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Section: Discussionsupporting

confidence: 81%

Extracellular vesicle protein levels are related to brain atrophy and cerebral white matter lesions in patients with manifest vascular disease: the SMART-MR study

et al. 2014

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“…Umegae et al . reported that CysC is upregulated in regressive astrocytes in a self‐defense response to the process of white matter degeneration in patients with WMH . Levy et al .…”

Section: Discussionmentioning

confidence: 99%

“…Umegae et al reported that CysC is upregulated in regressive astrocytes in a self-defense response to the process of white matter degeneration in patients with WMH. 28 Levy et al showed that CysC colocalized with amyloid-beta in parenchymal and vascular amyloid deposits in AD patient brains. 29 Furthermore, Sun et al reported that CysC regulates soluble amyloid-beta levels and is subsequently associated with neuronal deficits in a mouse model of AD.…”

Section: Discussionmentioning

confidence: 99%

Association of serum cystatin C with white matter abnormalities in patients with amnestic mild cognitive impairment

Hirao

Yamashita

Tsugawa

et al. 2019

Geriatrics Gerontology Int

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AimWhite matter hyperintensities (WMH) on MRI have been reported to be a risk factor for the conversion from mild cognitive impairment (MCI) to Alzheimer's disease, although the reason remains unclear. In the present study, we hence investigated the associations between WMH volumes and cognitive function, blood levels of various molecules, and the presence of lifestyle‐associated diseases in patients with amnestic MCI.MethodsThe initial data of 38 patients with amnestic MCI and 10 normal control individuals were analyzed. The volumes of periventricular hyperintensities (PVH) and deep WMH (DWMH) were measured on T2 fluid‐attenuated inversion recovery using the imaging software, 3D Slicer; and the association between PVH/DWMH volumes and cognitive function, blood levels of molecules (such as cystatin C [CysC], 25‐hydroxyvitamin D and homocysteine) and the presence of lifestyle‐associated diseases (such as hypertension, hyperlipidemia and diabetes mellitus) were analyzed.ResultsIn the MCI group, the PVH volume : intracranial volume ratio significantly correlated with Trail Making Test‐A/B scores and CysC level by Pearson's analysis, and the PVH volume : intracranial volume ratio significantly correlated with only CysC levels, whereas the DWMH volume : intracranial volume ratio did not correlate with any items at all by linear multiple regression analysis.ConclusionsPVH volume was closely associated with frontal lobe dysfunction, particularly with attention and executive dysfunction. Serum CysC level was associated with PVH volume, which suggests that CysC might be a useful marker for determining treatment strategies for white matter abnormalities in amnestic MCI. Geriatr Gerontol Int 2019; 19: 1036–1040.

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“…As multiple biological activities of CysC were found in the brain, much attention has been given to the relationship between CysC and the cause of neurological disease. In ischaemic WMLs, the CysC expression is upregulated in the regressive astrocytes, possibly a self-defense response in the process of white matter degeneration [23]. CysC regulates the extracellular matrix turnover resulting in the progressive formation of a cerebral arterial aneurysm [24].…”

Section: Discussionmentioning

confidence: 99%

Cystatin C as an index of cerebral small vessel disease: results of a cross‐sectional study in community‐based Japanese elderly

Wada

Nagasawa

Kawanami

et al. 2010

Euro J of Neurology

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Cystatin C expression in ischemic white matter lesions

Abstract: These results suggest that low levels of CSF cystatin C in ischemic WMLs might be due to the decreased number of astrocytes that secrete cystatin C in response to the stimuli of proteases and inflammatory cytokines.

Cited by 13 publications

References 33 publications

Extracellular vesicle protein levels are related to brain atrophy and cerebral white matter lesions in patients with manifest vascular disease: the SMART-MR study

Extracellular vesicle protein levels are related to brain atrophy and cerebral white matter lesions in patients with manifest vascular disease: the SMART-MR study

Association of serum cystatin C with white matter abnormalities in patients with amnestic mild cognitive impairment

Cystatin C as an index of cerebral small vessel disease: results of a cross‐sectional study in community‐based Japanese elderly

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