Oxidative imbalance and cathepsin D changes as peripheral blood biomarkers of Alzheimer disease: A pilot study

Straface, Elisabetta; Matarrese, Paola; Gambardella, Lucrezia; Vona, Rosa; Sgadari, Antonio; Silveri, Maria Caterina; Malorni, Walter

doi:10.1016/j.febslet.2005.03.094

Cited by 56 publications

(37 citation statements)

References 51 publications

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“…Patients with high serum CysC level indicated a onefold higher risk of DPN. As mentioned earlier, CysC was proved to be related to both CNS and peripheral nervous system diseases in several observational studies (13). Consistent with that, we found a significant increase in serum CysC levels in type 2 diabetic DPN patients.…”

Section: Discussionsupporting

confidence: 79%

“…It has been proved that CysC regulated the aggregation and deposition of amyloid b (12). And the serum CysC levels in patients with Alzheimer's disease were found be significantly higher than healthy controls (13). Moreover, change in the concentration of CysC in cerebrospinal fluid was also observed in demyelinating diseases including multiple sclerosis and Guillain Barre syndrome.…”

Section: Introductionmentioning

confidence: 83%

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Association between serum cystatin C and diabetic peripheral neuropathy: a cross-sectional study of a Chinese type 2 diabetic population

Liu

Shen

et al. 2014

European Journal of Endocrinology

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Objective: Serum cystatin C (CysC) is a sensitive marker of kidney function and recent studies have shown that CysC plays a critical role in degenerative diseases in both the central and the peripheral nervous systems. The aim of this study was to explore the relationship between serum CysC and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes. Methods: In total, 937 type 2 diabetic patients were enrolled in this cross-sectional study. Serum CysC concentration was measured by immunoturbidimetry. DPN was evaluated by neurological symptoms, neurological signs, neurothesiometer, and electromyogram. Results: Serum CysC levels were significantly higher in DPN patients (1.3 (1.1-1.5) mg/l) compared with patients with signs of DPN (1.1 (0.9-1.3) mg/l, P!0.001) and non-DPN patients (1.0 (0.9-1.3) mg/l, P!0.001). Multiple regression analysis revealed that DPN was associated with age, diabetes duration, HbA1c, and serum CysC. Spearman's correlation analysis showed that serum CysC was closely related with age, sex, diabetes duration, hypertension, glomerular infiltration rate, and serum creatinine (Cr) level. The patients were divided into quartiles according to the serum CysC levels. Compared with quartile 1 (referent), the risk of DPN was significantly higher in quartile 2 (odds ratio (OR), 1.753; 95% CI, 1.055-2.912; P!0.05), quartile 3 (OR, 2.463; 95% CI, 1.445-4.917; P!0.01), and quartile 4 (OR, 5.867; 95% CI, 2.075-16.589; P!0.01). Receiver-operating characteristic analysis revealed that the optimal cutoff point of serum CysC to indicate DPN was 1.25 mg/l in male patients and 1.05 mg/l in female patients. High serum CysC level indicated a onefold higher risk of DPN. Conclusions: High serum CysC level is closely associated with DPN and may be a potential biomarker for DPN in type 2 diabetic patients.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 83%

Association between serum cystatin C and diabetic peripheral neuropathy: a cross-sectional study of a Chinese type 2 diabetic population

Liu

Shen

et al. 2014

European Journal of Endocrinology

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“…This suggests that the fragment is generated via an alternative, non-amyloidogenic processing pathway. While definitive identification of this fragment will require isolation and amino acid sequencing, it has previously been reported that the activity of cathepsin D is decreased in the blood of AD subjects (Straface et al, 2005). Cathepsin D is an aspartyl protease that cleaves APP at a number of different sites (Higaki et al, 1996), including at Ser627, Phe765, Glu766, and Met768.…”

Section: Discussionmentioning

confidence: 99%

Blood-Borne Amyloid-β Dimer Correlates with Clinical Markers of Alzheimer's Disease

Villemagne¹,

Perez²,

Pike³

et al. 2010

J. Neurosci.

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Alzheimer's disease (AD) is the most common age-related dementia. Unfortunately due to a lack of validated biomarkers definitive diagnosis relies on the histological demonstration of amyloid-␤ (A␤) plaques and tau neurofibrillary tangles. A␤ processing is implicated in AD progression and many therapeutic strategies target various aspects of this biology. While A␤ deposition is the most prominent feature of AD, oligomeric forms of A␤ have been implicated as the toxic species inducing the neuronal dysfunction. Currently there are no methods allowing routine monitoring of levels of such species in living populations. We have used surface enhanced laser desorption ionization time of flight (SELDI-TOF) mass spectrometry incorporating antibody capture to investigate whether the cellular membranecontaining fraction of blood provides a new source of biomarkers. There are significant differences in the mass spectra profiles of AD compared with HC subjects, with significantly higher levels of A␤ monomer and dimer in the blood of AD subjects. Furthermore, levels of these species correlated with clinical markers of AD including brain A␤ burden, cognitive impairment and brain atrophy. These results indicate that fundamental biochemical events relevant to AD can be monitored in blood, and that the species detected may be useful clinical biomarkers for AD.

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“…In this context, the search for anomalous levels of free radical products facilitates the selection of biomarkers in AD. Several studies have shown that free radical products are present in the cerebrospinal fluid (CSF) of AD patients (Montine et al, 2002, Praticò et al, 1998, Strafacea et al, 2005. Nevertheless, CSF is not routinely collected in the evaluation of AD, and lumbar puncture is not a widespread procedure.…”

Section: Introductionmentioning

confidence: 99%

The lipid peroxidation products as possible markers of Alzheimer's disease in blood

Skoumalová

Ivica

Santorova

et al. 2011

Experimental Gerontology

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International audienceOxidative stress, which is present in Alzheimer's disease (AD), results in the formation of various end-products of free radical reactions with proteins and lipids. At present there are no reliable diagnostic biomarkers of AD in the blood. Therefore, specific products of lipid peroxidation in the blood of AD patients were investigated. Lipophilic extracts of erythrocytes in the group of patients with AD (n=44) and age-matched controls (n=16) were studied. The end-products of lipid peroxidation, so called lipofuscin-like pigments (LFP), were analyzed by fluorescence spectroscopy. It was found that the level of these products is significantly increased in erythrocytes of AD patients compared to controls. LFP were furher separated by means of HPLC into individual fractions to study their composition in AD and controls. The specific fraction of LFP in AD patients, which was isolated, might represent a disease-specific product in the blood

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Oxidative imbalance and cathepsin D changes as peripheral blood biomarkers of Alzheimer disease: A pilot study

Cited by 56 publications

References 51 publications

Association between serum cystatin C and diabetic peripheral neuropathy: a cross-sectional study of a Chinese type 2 diabetic population

Association between serum cystatin C and diabetic peripheral neuropathy: a cross-sectional study of a Chinese type 2 diabetic population

Blood-Borne Amyloid-β Dimer Correlates with Clinical Markers of Alzheimer's Disease

The lipid peroxidation products as possible markers of Alzheimer's disease in blood

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