| 1. |
- Kranaster, Laura, et al.
(författare)
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The novel seizure quality index for the antidepressant outcome prediction in electroconvulsive therapy: association with biomarkers in the cerebrospinal fluid.
- 2020
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Ingår i: European archives of psychiatry and clinical neuroscience. - : Springer Science and Business Media LLC. - 1433-8491 .- 0940-1334. ; 270:7, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- For patients with depression treated with electroconvulsive therapy (ECT), the novel seizure quality index (SQI) can predict the risk of non-response (and non-remission)-as early as after the second ECT session-based the extent of several ictal parameters of the seizure. We aim to test several CSF markers on their ability to predict the degree of seizure quality, measured by the SQI to identify possible factors, that could explain some variability of the seizure quality. Baseline CSF levels of metabolites from the kynurenine pathway, markers of neurodegeneration (tau proteins, β-amyloids and neurogranin), elements of the innate immune system, endocannabinoids, sphingolipids, neurotrophic factors (VEGF) and Klotho were measured before ECT in patients with depression (n=12) to identify possible correlations with the SQI by Pearson's partial correlation. Negative, linear relationships with the SQI for response were observed for CSF levels of T-tau (rpartial=-0.69, p=0.019), phosphatidylcholines (rpartial=-0.52, p=0.038) and IL-8 (rpartial=-0.67, p=0.047). Regarding the SQI for remission, a negative, linear relationship was noted with CSF levels of the endocannabinoid AEA (rpartial=-0.70, p=0.024) and CD163 (rpartial=-0.68, p=0.029). In sum, CSF Markers for the innate immune system, for neurodegeneration and from lipids were found to be associated with the SQI for response and remission after adjusting for age. Consistently, higher CSF levels of the markers were always associated with lower seizure quality. Based on these results, further research regarding the mechanism of seizure quality in ECT is suggested.
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| 2. |
- Lewczuk, Piotr, et al.
(författare)
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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.
- 2018
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Ingår i: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. - : Informa UK Limited. - 1814-1412. ; 19:4, s. 244-328
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Tidskriftsartikel (refereegranskat)abstract
- In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
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| 3. |
- Llorens, Franc, et al.
(författare)
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Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The clinical diagnosis of vascular dementia (VaD) is based on imaging criteria, and specific biochemical markers are not available. Here, we investigated the potential of cerebrospinal fluid (CSF) lipocalin 2 (LCN2), a secreted glycoprotein that has been suggested as mediating neuronal damage in vascular brain injuries. The study included four independent cohorts with a total n=472 samples. LCN2 was significantly elevated in VaD compared to controls, Alzheimers disease (AD), other neurodegenerative dementias, and cognitively unimpaired patients with cerebrovascular disease. LCN2 discriminated VaD from AD without coexisting VaD with high accuracy. The main findings were consistent over all cohorts. Neuropathology disclosed a high percentage of macrophages linked to subacute infarcts, reactive astrocytes, and damaged blood vessels in multi-infarct dementia when compared to AD. We conclude that CSF LCN2 is a promising candidate biochemical marker in the differential diagnosis of VaD and neurodegenerative dementias. Diagnosis of vascular dementia is hampered by the lack of biochemical markers for this disease. Here, the authors show that vascular dementia is associated with increased lipocalin-2 in cerebrospinal fluid, compared to controls and patients with other forms of dementia.
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| 4. |
- Szegő, Éva M., et al.
(författare)
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Cytosolic Trapping of a Mitochondrial Heat Shock Protein Is an Early Pathological Event in Synucleinopathies
- 2019
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:1, s. 6-77
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-synuclein (aSyn) accumulates in intracellular inclusions in synucleinopathies, but the molecular mechanisms leading to disease are unclear. We identify the 10 kDa heat shock protein (HSP10) as a mediator of aSyn-induced mitochondrial impairments in striatal synaptosomes. We find an age-associated increase in the cytosolic levels of HSP10, and a concomitant decrease in the mitochondrial levels, in aSyn transgenic mice. The levels of superoxide dismutase 2, a client of the HSP10/HSP60 folding complex, and synaptosomal spare respiratory capacity are also reduced. Overexpression of HSP10 ameliorates aSyn-associated mitochondrial dysfunction and delays aSyn pathology in vitro and in vivo. Altogether, our data indicate that increased levels of aSyn induce mitochondrial deficits, at least partially, by sequestering HSP10 in the cytosol and preventing it from acting in mitochondria. Importantly, these alterations manifest first at presynaptic terminals. Our study not only provides mechanistic insight into synucleinopathies but opens new avenues for targeting underlying cellular pathologies. Szegő et al. identify HSP10 as a modulator of alpha-synuclein-induced mitochondrial impairment in striatal synaptosomes. Age-associated increase in the cytosolic and decrease in mitochondrial levels of HSP10 results in a reduction in the levels of SOD2 and of synaptosomal ATP production on demand. HSP10 overexpression delays alpha-synuclein pathology both in vitro and in vivo.
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| 5. |
- Zerr, Inga, et al.
(författare)
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Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases.
- 2018
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 14:6, s. 751-763
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown.Cerebrospinal fluid NFL levels were quantified in nonprimarily neurodegenerative neurological and psychiatric diseases (n=122), mild cognitive impairment (n=48), Alzheimer's disease (n=108), dementia with Lewy bodies/Parkinson's disease dementia (n=53), vascular dementia (n=46), frontotemporal dementia (n=41), sporadic Creutzfeldt-Jakob disease (sCJD, n=132), and genetic prion diseases (n=182).The highest NFL levels were detected in sCJD, followed by vascular dementia, frontotemporal dementia, dementia with Lewy bodies/Parkinson's disease dementia, Alzheimer's disease, and mild cognitive impairment. In sCJD, NFL levels correlated with cerebrospinal fluid tau and disease duration. NFL levels were able to differentiate sCJD from nonprimarily neurodegenerative neurological and psychiatric diseases (area under the curve=0.99, 95% confidence interval: 0.99-1) and from the other diagnostic groups showing cognitive impairment/dementia of a non-CJD etiology (area under the curve=0.90, 95% confidence interval: 0.87-0.92). Compared to nonprimarily neurodegenerative neurological and psychiatric diseases, NFL was also elevated in genetic prion diseases associated with the E200K, V210I, P102L, and D178N prion protein gene mutations.Increased NFL levels are a common feature in neurodegenerative dementias.
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