CSF Ubiquitin Levels Are Higher in Alzheimer’s Disease than in Frontotemporal Dementia and Reflect the Molecular Subtype in Prion Disease

Abu‐Rumeileh, Samir; Oeckl, Patrick; Baiardi, Simone; Halbgebauer, Steffen; Steinacker, Petra; Capellari, Sabina; Otto, Markus; Parchi, Piero

doi:10.3390/biom10040497

Cited by 11 publications

(12 citation statements)

References 35 publications

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“…Many of these markers are universal across NDDs, supporting the idea of a common neuroinflammatory profile across these diseases. Some of these common neuroinflammation mediators are chitotriosidase 1 (CHIT1), chitinase-3-like protein 1 (YKL-40), the glial fibrillary acidic protein (GFAP) and important pro-inflammatory cytokines, such as interleukin-1β (IL-1), IL-6 and tumor necrosis factor α (TNF-α) [ 41 , 42 ].…”

Section: Neuroinflammation As a Common Factor Across Neurodegeneramentioning

confidence: 99%

Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

González-Sanmiguel

Schuh

Muñoz-Montesino

et al. 2020

Cells

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Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Creutzfeldt–Jakob disease (CJD) are brain conditions affecting millions of people worldwide. These diseases are associated with the presence of amyloid-β (Aβ), alpha synuclein (α-Syn) and prion protein (PrP) depositions in the brain, respectively, which lead to synaptic disconnection and subsequent progressive neuronal death. Although considerable progress has been made in elucidating the pathogenesis of these diseases, the specific mechanisms of their origins remain largely unknown. A body of research suggests a potential association between host microbiota, neuroinflammation and dementia, either directly due to bacterial brain invasion because of barrier leakage and production of toxins and inflammation, or indirectly by modulating the immune response. In the present review, we focus on the emerging topics of neuroinflammation and the association between components of the human microbiota and the deposition of Aβ, α-Syn and PrP in the brain. Special focus is given to gut and oral bacteria and biofilms and to the potential mechanisms associating microbiome dysbiosis and toxin production with neurodegeneration. The roles of neuroinflammation, protein misfolding and cellular mediators in membrane damage and increased permeability are also discussed.

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Section: Neuroinflammation As a Common Factor Across Neurodegeneramentioning

confidence: 99%

Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

González-Sanmiguel

Schuh

Muñoz-Montesino

et al. 2020

Cells

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“…Demographic and clinical data of the sCJD cohort are shown in Supplementary Table S3. For the analysis according to the sCJD molecular subtypes, we merged the subjects with definite sCJD (28 MM(V)1, 15 VV2 and 13 MV2K) with those with a probable sCJD diagnosis (five VV2 and two MV2K) and a high level of certainty for a given subtype as described [22]. In each case, we calculated the length of survival and the disease stage as described [23].…”

Section: Patient Selection Csf and Neuropathological Analysesmentioning

confidence: 99%

“…In each case, we calculated the length of survival and the disease stage as described [23]. The control group included 25 subjects lacking any clinical or neuroradiologic evidence of central nervous system disease and having CSF p-tau, t-tau and Aβ42 in the normal range [22].…”

Section: Patient Selection Csf and Neuropathological Analysesmentioning

confidence: 99%

“…A detailed description of the sample preparation and MRM method is provided in the Supplementary Methods and Table S4. CSF t-tau, protein 14-3-3, NfL and YKL-40 were analyzed in the sCJD group and AD core biomarkers in the control group at the NP-Lab of Bologna using commercially available ELISA kits as already published [22]. PrP Sc seeding activity was detected by RT-QuIC [20,21].…”

Section: Patient Selection Csf and Neuropathological Analysesmentioning

confidence: 99%

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Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease

Abu‐Rumeileh

Barschke

Oeckl

et al. 2022

IJMS

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Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, no study to date investigated these peptides in the CSF of sporadic Creutzfeldt–Jakob disease (sCJD). Using liquid chromatography-multiple reaction monitoring mass spectrometry, we evaluated the CSF PDYN- and PENK-derived peptide levels in 25 controls and 63 patients with sCJD belonging to the most prevalent molecular subtypes (MM(V)1, VV2 and MV2K). One of the PENK-derived peptides was significantly decreased in each sCJD subtype compared to the controls without a difference among subtypes. Conversely, PDYN-derived peptides were selectively decreased in the CSF of sCJD MV2K, a subtype with a more widespread overall pathology compared to the sCJD MM(V)1 and the VV2 subtypes, which we confirmed by semiquantitative analysis of cortical and striatal neuronal loss and astrocytosis. In sCJD CSF PENK and PDYN were associated with CSF biomarkers of neurodegeneration but not with clinical variables and showed a poor diagnostic performance. CSF PDYN and PENK-derived peptides had no significant diagnostic and prognostic values in sCJD; however, the distinct marker levels between molecular subtypes might help to better understand the basis of phenotypic heterogeneity determined by divergent neuronal targeting.

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“…It has been speculated that neurogranin levels could be useful to differentiate between different subtypes of CJD (different concentrations having reported according to the clinicopathological subtypes) [4]. Interestingly, it has been reported that ubiquitin, which marks neuritic damage, dysfunctional protostasis and neuroinflammation, has higher concentrations in CJD than in controls and other neurodegenerative dementias, and especially in less frequent forms of sCJD such as MM(V)1 [64,65]. One study has also shown higher levels of calmodulin, a ubiquitous calcium-binding protein, in sCJD compared to other neurodegenerative dementias particularly in those with higher levels of t-tau [66].…”

Section: Other Biomarkersmentioning

confidence: 99%

Role of Biomarkers for the Diagnosis of Prion Diseases

Altuna¹,

Ruiz²,

Zelaya³

et al. 2022

Preprint

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Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5–2 cases per million per year). Genetic (10-15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram) and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests such as RT-QuIC is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt-Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain among others) to try to universalize access to early diagnosis in the case of prion diseases.

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CSF Ubiquitin Levels Are Higher in Alzheimer’s Disease than in Frontotemporal Dementia and Reflect the Molecular Subtype in Prion Disease

Cited by 11 publications

References 35 publications

Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease

Role of Biomarkers for the Diagnosis of Prion Diseases

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