| 1. |
- Lindqvist, Daniel, et al.
(författare)
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Cerebrospinal fluid inflammatory markers in Parkinson's disease - Associations with depression, fatigue, and cognitive impairment.
- 2013
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Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 1090-2139 .- 0889-1591. ; 33:Jul.,31, s. 183-189
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation may be involved in the pathophysiology of Parkinson's disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. The aim of this study was to measure inflammatory markers in cerebrospinal fluid (CSF) samples from PD patients and a reference group, and to investigate correlations between non-motor symptoms and inflammation. We quantified C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein 1-β in CSF samples from PD patients (N=87) and the reference group (N=33). Sixteen of the PD patients had a dementia diagnosis (PDD). We assessed symptoms of fatigue, depression, anxiety and cognitive function using the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and the Mini Mental State Examination, respectively. There were no significant differences in mean levels of inflammatory markers between PD patients and the reference group. After controlling for age, gender and somatic illness, patients with PDD had significantly higher levels of CRP compared to non-demented PD patients (p=0.032) and the reference group (p=0.026). Increased levels of inflammatory markers in CSF were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition in the entire PD group. After controlling for PD duration, age, gender, somatic illness and dementia diagnosis, high CRP levels were significantly associated with more severe symptoms of depression (p=0.010) and fatigue (p=0.008), and high MCP-1 levels were significantly associated with more severe symptoms of depression (p=0.032). Our results indicate that non-motor features of PD such as depression, fatigue, and cognitive impairment are associated with higher CSF levels of inflammatory markers.
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| 2. |
- Nielsen, Henrietta, et al.
(författare)
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Low levels of soluble NG2 in cerebrospinal fluid from patients with dementia with Lewy bodies
- 2014
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 40:2, s. 343-350
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Tidskriftsartikel (refereegranskat)abstract
- The proteoglycan NG2 plays a major role in proliferation, migration, and differentiation of pericytes and NG2 cells in the brain. We have previously reported decreased soluble NG2 (sNG2) levels in cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) and a relationship between sNG2 and AD biomarkers in these patients. To further investigate whether alterations in sNG2 is specific to AD pathology, we measured levels of sNG2 in CSF from a patient cohort consisting of non-demented controls (n = 51), patients with Parkinson's disease (PD) (n = 61), and patients with dementia with Lewy bodies (DLB) (n = 37), two synucleinopathies whereof the latter disorder frequently coincides with amyloid-β pathology similar to AD. We found decreased sNG2 concentrations in DLB patients, but not in PD patients, compared to controls. Levels of sNG2 in controls and PD patients correlated to T-tau, P-tau, α-synuclein, and neurosin. Only one correlation, between sNG2 and neurosin, was found in DLB patients. Analysis of a second cohort consisting of controls (n = 23) and DLB patients (n = 31) showed that the result was reproducible, as lower levels of sNG2 again were found in DLB patients compared to controls. We conclude that lower levels of sNG2 levels indicate a DLB-related impact on NG2 expressing cells foremost associated with neuropathology linked to accumulation of amyloid-β and not α-synuclein.
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| 3. |
- Wennström, Malin, et al.
(författare)
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Low CSF Levels of Both α-Synuclein and the α-Synuclein Cleaving Enzyme Neurosin in Patients with Synucleinopathy.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Neurosin is a protease that in vitro degrades α-synuclein, the main constituent of Lewy bodies found in brains of patients with synucleinopathy including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Several studies have reported reduced cerebrospinal fluid (CSF) levels of α-synuclein in synucleinopathy patients and recent data also proposes a significant role of α-synuclein in the pathophysiology of Alzheimer's disease (AD). To investigate potential links between neurosin and its substrate α-synuclein in vivo we used a commercially available sandwich ELISA and an in-house developed direct ELISA to quantify CSF levels of α-synuclein and neurosin in patients diagnosed with DLB, PD and PD dementia (PDD) versus AD patients and non-demented controls. We found that patients with synucleinopathy displayed lower CSF levels of neurosin and α-synuclein compared to controls and AD patients. In contrast, AD patients demonstrated significantly increased CSF α-synuclein but similar neurosin levels compared to non-demented controls. Further, CSF neurosin and α-synuclein concentrations were positively associated in controls, PD and PDD patients and both proteins were highly correlated to CSF levels of phosphorylated tau in all investigated groups. We observed no effect of gender or presence of the apolipoprotein Eε4 allele on neither neurosin or α-synuclein CSF levels. In concordance with the current literature our study demonstrates decreased CSF levels of α-synuclein in synucleinopathy patients versus AD patients and controls. Importantly, decreased α-synuclein levels in patients with synucleinopathy appear linked to low levels of the α-synuclein cleaving enzyme neurosin. In contrast, elevated levels of α-synuclein in AD patients were not related to any altered CSF neurosin levels. Thus, altered CSF levels of α-synuclein and neurosin in patients with synucleinopathy versus AD may not only mirror disease-specific neuropathological mechanisms but may also serve as fit candidates for future biomarker studies aiming at identifying specific markers of synucleinopathy.
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| 4. |
- Wennström, Malin, et al.
(författare)
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The Inflammatory Marker YKL-40 Is Elevated in Cerebrospinal Fluid from Patients with Alzheimer's but Not Parkinson's Disease or Dementia with Lewy Bodies.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- A major difference in the revised diagnostic criteria for Alzheimer's disease (AD) is the incorporation of biomarkers to support a clinical diagnosis and allow the identification of preclinical AD due to AD neuropathological processes. However, AD-specific fluid biomarkers which specifically distinguish clinical AD dementia from other dementia disorders are still missing. Here we aimed to evaluate the disease-specificity of increased YKL-40 levels in cerebrospinal fluid (CSF) from AD patients with mild to moderate dementia (n = 49) versus Parkinson's disease (PD) (n = 61) and dementia with Lewy bodies (DLB) patients (n = 36), and non-demented controls (n = 44). Second we aimed to investigate whether altered YKL-40 levels are associated with CSF levels of other inflammation-associated molecules. When correcting for age, AD patients exhibited 21.3%, 27.7% and 38.8% higher YKL-40 levels compared to non-demented controls (p = 0.0283), DLB (p = 0.0027) and PD patients (p<0.0001). The AD-associated increase in YKL-40 was not associated with CSF P-tau, T-tau or Aβ42. No relationship between increased YKL-40 and levels of the astrocytic marker glial-fibrillary acidic protein (GFAP), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and interferon gamma-induced protein 10 (IP-10) could be identified. Our results confirm previous reports of an age-associated increased in CSF YKL-40 levels and further demonstrate increased CSF YKL-40 in AD patients versus non-demented controls and patients with DLB or PD. The increase in YKL-40 levels in the AD patients was unrelated to the established CSF AD biomarkers and the inflammatory markers GFAP, MCP-1, IP-10 and IL-8, proposing YKL-40 as a marker of yet to be identified AD-related pathological processes.
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