The cerebrospinal fluid oxidized NO metabolites, nitrite and nitrate, in Alzheimer's disease and vascular dementia of Binswanger type and multiple small infarct type

Background: Brevican and neurocan are central nervous system-specific extracellular matrix proteoglycans. They are degraded by extracellular enzymes, such as metalloproteinases. However, their degradation profile is largely unexplored in cerebrospinal fluid (CSF). Objective: The study aim was to quantify proteolytic peptides derived from brevican and neurocan in human CSF of patients with Alzheimer’s disease (AD) and vascular dementia (VaD) compared with controls. Methods: The first cohort consisted of 75 individuals including 25 patients with AD, 7 with mild cognitive impairment (MCI) diagnosed with AD upon follow-up, 10 patients with VaD or MCI diagnosed with VaD upon follow-up, and 33 healthy controls and cognitively stable MCI patients. In the second cohort, 31 individuals were included (5 AD patients, 14 VaD patients and 12 healthy controls). Twenty proteolytic peptides derived from brevican (n = 9) and neurocan (n = 11) were quantified using high-resolution parallel reaction monitoring mass spectrometry. Results: In the first cohort, the majority of CSF concentrations of brevican and neurocan peptides were significantly decreased inVaDas compared withADpatients (AUC = 0.83.0.93, p≤0.05) and as compared with the control group (AUC = 0.79.0.87, p ≤ 0.05). In the second cohort, CSF concentrations of two brevican peptides (B87, B156) were significantly decreased in VaD compared with AD (AUC = 0.86.0.91, p ≤ 0.05) and to controls (AUC = 0.80.0.82, p ≤ 0.05), while other brevican and neurocan peptides showed a clear trend to be decreased in VaD compared with AD (AUC = 0.64.80, p > 0.05). No peptides differed between AD and controls. Conclusion: Brevican and neurocan peptides are potential diagnostic biomarkers for VaD, with ability to separate VaD from AD.

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Cerebrospinal Fluid Amyloid ss42/Phosphorylated Tau Ratio Discriminates Between Alzheimer's Disease and Vascular Dementia

The Journals of Gerontology Series A ◽

10.1093/gerona/61.7.755 ◽

2006 ◽

Vol 61 (7) ◽

pp. 755-758 ◽

Cited By ~ 66

Author(s):

D. de Jong ◽

R. W. M. M. Jansen ◽

B. P. H. Kremer ◽

M. M. Verbeek

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Vascular Dementia ◽

Phosphorylated Tau

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Cerebrospinal Fluid Phospho-Tau, Total Tau and β-Amyloid1–42 in the Differentiation between Alzheimer’s Disease and Vascular Dementia

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000066023 ◽

2002 ◽

Vol 14 (4) ◽

pp. 183-190 ◽

Cited By ~ 38

Author(s):

Katarina Nägga ◽

Johan Gottfries ◽

Kaj Blennow ◽

Jan Marcusson

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Vascular Dementia ◽

Total Tau ◽

Β Amyloid

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Arylesterase Activity of Paraoxonase-1 in Serum and Cerebrospinal Fluid of Patients with Alzheimer’s Disease and Vascular Dementia

Antioxidants ◽

10.3390/antiox9050456 ◽

2020 ◽

Vol 9 (5) ◽

pp. 456 ◽

Cited By ~ 2

Author(s):

Arianna Romani ◽

Alessandro Trentini ◽

Wiesje M. van der Flier ◽

Tiziana Bellini ◽

Giovanni Zuliani ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Vascular Dementia ◽

Apolipoprotein A1 ◽

Paraoxonase 1 ◽

Imaging Biomarkers ◽

Composite Parameter ◽

Older Subjects ◽

T Tau

Background: It has been suggested that circulating Paraoxonase-1 (PON1) and apolipoprotein A1 (APOA1), which closely interacts with the antioxidant enzyme, could be implicated in Alzheimer’s disease (AD) and vascular dementia (VaD) development. This study aimed to evaluate PON1 changes in serum and cerebrospinal fluid (CSF) as evidence for its association with AD or VaD. Methods: Serum PON-arylesterase activity was measured in patients with AD, VaD, and CONTROLS distributed in two cohorts: Ferrara cohort (FC: n = 503, age = 74 years) and Amsterdam Dementia cohort (ADC: n = 71, age = 65 years). In the last cohort, CSF PON-arylesterase, CSF β-amyloid1-42, p-tau and t-tau, and imaging biomarkers were also measured. Results: AD and VaD patients of FC showed significantly lower levels of serum PON-arylesterase compared to CONTROLS, but this outcome was driven by older subjects (>71 years, p < 0.0001). In the younger ADC, a similar decreasing (but not significant) trend was observed in serum and CSF. Intriguingly, PON-arylesterase per APOA1 correlated with t-tau in AD group (r = −0.485, p = 0.002). Conclusion: These results suggest that decreased peripheral PON-arylesterase might be a specific feature of older AD/VaD patients. Moreover, we showed that PON-arylesterase/APOA1 is inversely related to neurodegeneration in AD patients, suggesting a prognostic usefulness of this composite parameter.

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Ubiquitin in Cerebrospinal Fluid in Alzheimer's Disease and Vascular Dementia

International Psychogeriatrics ◽

10.1017/s1041610294001584 ◽

1994 ◽

Vol 6 (1) ◽

pp. 13-22 ◽

Cited By ~ 28

Author(s):

Kaj Blennow ◽

Pia Davidsson ◽

Anders Wallin ◽

Carl-Gerhard Gottfries ◽

Lars Svennerholm

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Vascular Dementia ◽

Enzyme Linked Immunosorbent Assay ◽

Specific Marker ◽

Albumin Ratio ◽

Control Value ◽

Proteolytic Pathway ◽

The Mean

Ubiquitin (Ub) was determined by a competitive enzyme-linked immunosorbent assay (ELISA) in serum (S) and cerebrospinal fluid (CSF) samples from 29 patients with ‘probable Alzheimer's disease’ (AD), 14 patients with vascular dementia (VAD), and 13 healthy individuals. The mean concentration of Ub in CSF (110 ± 20 ng/mL) was about 20% of that in serum (940 ± 120 ng/mL) in healthy controls. There was no significant correlation between S-Ub and CSF-Ub, or between the CSF/S Ub ratio and the CSF/S albumin ratio. These findings suggest that a major portion of CSF-Ub is intrathecally produced. CSF-Ub was increased while S-Ub was decreased in both AD and VAD patients as compared with controls. As a consequence, the CSF/S Ub ratio showed good discrimination between patients and controls: 22/29 (76%) of the AD patients and 9/14 (64%) of the VAD patients had a CSF/S Ub ratio that was higher than the highest control value. No significant differences in any of the parameters were found between AD and VAD. Ub is involved in an ATP-dependent proteolytic pathway and also acts as a heatshock protein. The increase in CSF-Ub in AD and VAD may therefore be interpreted as a cytoprotective response to abnormal or damaged proteins, and CSF-Ub may have a potential as a non-disease-specific marker for cerebral degeneration.

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