Highlights
- •A case–control study about UCH-L1 in serum and urine of patients with WMLs
- •Serum UCH-L1 levels were independently associated with the severity of WMLs.
- •Urine UCH-L1 levels were similar between WML group and controls.
- •Serum UCH-L1 levels in S-WML group were higher than P-WML group.
Abstract
Objectives
Ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has been established as a potential
biomarker of neuronal damage. There is not much information about the effects of white
matter lesions (WMLs) on serum and urine UCH-L1 levels in white matter disease patients.
This study was aimed to assess whether serum or urine UCH-L1 levels are a reliable
marker of brain damage in patients with WMLs.
Design and methods
Serum and urine levels of UCH-L1 were assessed in 125 patients with dizziness, hypertension,
type 2 diabetes mellitus, or dyslipidemia. Of these 125 patient cases, 41 showed periventricular
WMLs (P-WMLs), 46 showed subcortical WMLs (S-WMLs), and 38 displayed no well-defined
WMLs (controls).
Results
Serum UCH-L1 levels were significantly different between the WML group and controls
(p < 0.05). Further subgroup analysis proved that serum UCH-L1 levels in participants with
S-WMLs were significantly increased when compared with controls (p < 0.001), but there was no significant differences between controls and patients with
P-WMLs (p > 0.05). However, urine levels of UCH-L1 were similar between these three groups (p > 0.05). In addition, multivariate analysis showed that increased serum UCH-L1 levels
were independently associated with the severity of WMLs using Fazekas scale (β = 0.432, p < 0.001).
Conclusions
These findings suggest that serum UCH-L1 levels may serve as a novel biomarker for
neuronal damage from WMLs, especially S-WMLs.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Potential role of blood biomarkers in the management of nontraumatic intracerebral hemorrhage.Cerebrovasc. Dis. 2014; 38: 395-409
- Neurobiochemical markers of brain damage in cerebrospinal fluid of acute ischemic stroke patients.Clin. Chem. 2010; 56: 451-458
- Role of S100B protein in urine and serum as an early predictor of mortality after severe traumatic brain injury in adults.Clin. Chim. Acta. 2012; 414: 228-233
- The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase.Science. 1989; 246: 670-673
- Ubiquitin and the synapse.Nat. Rev. Neurosci. 2002; 3: 854-861
- A mouse model of Rubinstein–Taybi syndrome: defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4.Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 10518-10522
- Endogenous neurotoxic dopamine derivative covalently binds to Parkinson's disease-associated ubiquitin C-terminal hydrolase L1 and alters its structure and function.J. Neurochem. 2014; 130: 826-838
- Membrane-associated farnesylated UCH-L1 promotes α-synuclein neurotoxicity and is a therapeutic target for Parkinson's disease.Proc. Natl. Acad. Sci. U. S. A. 2009; 106: 4635-4640
- Ab1-42-mediated down-regulation of Uch-L1 is dependent on NF-κB activation and impaired BACE1 lysosomal degradation.Aging Cell. 2012; 11: 834-844
- Disturbed sleep/wake rhythms and neuronal cell loss in lateral hypothalamus and retina of mice with a spontaneous deletion in the ubiquitin carboxyl-terminal hydrolase L1 gene.Neurobiol. Aging. 2012; 33: 393-403
- Mutation analysis and association studies of the ubiquitin carboxy-terminal hydrolase L1 gene in Huntington's disease.Neurosci. Lett. 2002; 328: 1-4
- Cerebrospinal fluid ubiquitin C-terminal hydrolase as a novel marker of neuronal damage after epileptic seizure.Epilepsy Res. 2013; 103: 205-210
- Different expression of ubiquitin C-terminal hydrolase-L1 and αII-spectrin in ischemic and hemorrhagic stroke: potential biomarkers in diagnosis.Brain Res. 2013; 1540: 84-91
- Identification and preliminary characterization of ubiquitin C terminal hydrolase 1 (UCHL1) as a biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage.J. Neurosci. Res. 2010; 88: 1475-1484
- Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein.J. Neurotrauma. 2014; 31: 19-25
- Cerebral white matter lesions in patients with dementia — from MCI to severe Alzheimer's disease.J. Neurol. Sci. 2009; 283: 79-82
- Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study.J. Neurol. Neurosurg. Psychiatry. 2001; 70: 9-14
- White matter lesions in Parkinson disease.Nat. Rev. Neurol. 2011; 7: 229-236
- Regional white matter lesions predict falls in patients with amnestic mild cognitive impairment and Alzheimer's disease.J. Am. Med. Dir. Assoc. 2014; 15: 36-41
- Psychosis and epileptic seizures in Wilson's disease with predominantly white matter lesions in the frontal lobe.Parkinsonism Relat. Disord. 1995; 1: 53-58
- Severity of leukoaraiosis, leptomeningeal collaterals, and clinical outcomes after intra-arterial therapy in patients with acute ischemic stroke.J. Neurointerv. Surg. 2014; https://doi.org/10.1136/neurintsurg-2013-011083
- Diffusion tensor imaging and white matter lesions at the subacute stage in mild traumatic brain injury with persistent neurobehavioral impairment.Hum. Brain Mapp. 2011; 32: 999-1011
- Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study.Ann. Neurol. 2000; 47: 145-151
- MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging.AJR Am. J. Roentgenol. 1987; 149: 351-356
- Vitamin D and white matter abnormalities in older adults: a cross-sectional neuroimaging study.Eur. J. Neurol. 2014; 21: 1436-1442
- Vascular pathology in the aged human brain.Acta Neuropathol. 2010; 119: 277-290
- The effect of white matter lesions on cognition after carotid revascularization.J. Neurol. Sci. 2013; 334: 77-82
- Pathogenesis of leukoaraiosis: a review.Stroke. 1997; 28: 652-659
- Blood–brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis.J. Neurol. Neurosurg. Psychiatry. 2010; 81: 192-197
- Cerebrovascular biomarker profile is related to white matter disease and ventricular dilation in a LADIS substudy.Dement. Geriatr. Cogn. Dis. Extra. 2014; 4: 385-394
- Mild cognitive impairment: cerebrospinal fluid tau biomarker pathologic levels and longitudinal changes in white matter integrity.Radiology. 2013; 266: 295-303
- Symptoms, vascular risk factors and blood–brain barrier function in relation to CT white-matter changes in dementia.Eur. Neurol. 2000; 44: 229-235
- Glial fibrillary acidic protein as a biomarker for periventricular white matter injury.Am. J. Obstet. Gynecol. 2013; 209: 27.e1-27.e7
- S100beta as a predictor of brain metastases: brain versus cerebrovascular damage.Cancer. 2005; 104: 817-824
- Small vessel ischemic disease of the brain and brain metastases in lung cancer patients.PLoS One. 2009; 4: e7242
- Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients.J. Neurol. 2013; 260: 2642-2649
- Serum biomarkers in white matter disease (Wmd)—a preliminary study.Clin. Biochem. 2011; 44: 1168
- Urinary albumin to creatinine ratio as potential biomarker for cerebral microvascular disease.Curr. Neurovasc. Res. 2014; 11: 242-247
- Significance of ubiquitin carboxy-terminal hydrolase L1 elevations in athletes after sub-concussive head hits.PLoS One. 2014; 9: e96296
- A pilot study of novel biomarkers in neonates with hypoxic–ischemic encephalopathy.Pediatr. Res. 2010; 68: 531-536
- Stress and depression: possible links to neuron death in the hippocampus.Bipolar Disord. 2002; 4: 117-128
- Ventriculomegaly and balance disturbances in patients with TIA.Acta Neurol. Scand. 2012; 125: 163-170
- Neuroprotective effect of memantine on hippocampal neurons in infantile rat hydrocephalus.Turk. Neurosurg. 2011; 21: 352-358
- Cerebrospinal fluid markers of neurodegeneration and rates of brain atrophy in early Alzheimer disease.JAMA Neurol. 2015; 72: 656-665
- Thalamic diffusion differences related to cognitive function in white matter lesions.Neurobiol. Aging. 2014; 35: 1103-1110
- Regional white matter pathology in mild cognitive impairment: differential influence of lesion type on neuropsychological functioning.Stroke. 2008; 39: 794-799
- White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury.Stroke. 2006; 37: 1391-1398
- Cerebrospinal fluid and urinary biomarkers in multiple sclerosis.Acta Neurol. Scand. 2013; 128: 321-327
- A new role for the neuronal ubiquitin C-terminal hydrolase-L1 (UCH-L1) in podocyte process formation and podocyte injury in human glomerulopathies.J. Pathol. 2009; 217: 452-464
- Protein gene product 9.5 and ubiquitin are expressed in metabolically active epithelial cells of normal and pathologic human kidney.Nephrol. Dial. Transplant. 2005; 20: 2714-2719
Article info
Publication history
Published online: July 23, 2015
Accepted:
July 21,
2015
Received in revised form:
June 17,
2015
Received:
February 6,
2015
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
