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Sökning: WFRF:(Rosén Christoffer 1986)

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1.
  • Rosén, Christoffer, 1986, et al. (författare)
  • Fluid biomarkers in Alzheimer's disease - current concepts
  • 2013
  • Ingår i: Molecular Neurodegeneration. - : BioMed Central (BMC). - 1750-1326. ; 8:20
  • Tidskriftsartikel (refereegranskat)abstract
    • The diagnostic guidelines of Alzheimer's disease (AD) have recently been updated to include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. The CSF biomarkers total tau (T-tau), hyperphosphorylated tau (P-tau) and the 42 amino acid isoform of amyloid beta (A beta 42) reflect the core pathologic features of AD, which are neuronal loss, intracellular neurofibrillary tangles and extracellular senile plaques. Since the pathologic processes of AD start decades before the first symptoms, these biomarkers may provide means of early disease detection. The updated guidelines identify three different stages of AD: preclinical AD, mild cognitive impairment (MCI) due to AD and AD with dementia. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review results from blood biomarker studies. In summary, the core AD CSF biomarkers have high diagnostic accuracy both for AD with dementia and to predict incipient AD (MCI due to AD). Longitudinal studies on healthy elderly and recent cross-sectional studies on patients with dominantly inherited AD mutations have also found biomarker changes in cognitively normal at-risk individuals. This will be important if disease-modifying treatment becomes available, given that treatment will probably be most effective early in the disease. An important prerequisite for this is trustworthy analyses. Since measurements vary between studies and laboratories, standardization of analytical as well as pre-analytical procedures will be essential. This process is already initiated. Apart from filling diagnostic roles, biomarkers may also be utilized for prognosis, disease progression, development of new treatments, monitoring treatment effects and for increasing the knowledge about pathologic processes coupled to the disease. Hence, the search for new biomarkers continues. Several candidate biomarkers have been found in CSF, and although biomarkers in blood have been harder to find, some recent studies have presented encouraging results. But before drawing any major conclusions, these results need to be verified in independent studies.
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2.
  • Skillbäck, Tobias, et al. (författare)
  • CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival.
  • 2014
  • Ingår i: Neurology. - : American Academy of Neurology. - 1526-632X .- 0028-3878. ; 83:21, s. 1945-53
  • Tidskriftsartikel (refereegranskat)abstract
    • We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis.
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3.
  • Rosén, Christoffer, 1986, et al. (författare)
  • Cerebrospinal fluid biomarkers in cardiac arrest survivors.
  • 2014
  • Ingår i: Resuscitation. - 1873-1570. ; 85:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the levels of various cerebrospinal fluid (CSF) biomarkers related to neuronal damage, inflammation and amyloid β (Aβ) metabolism in patients resuscitated after an out-of-hospital cardiac arrest (CA).
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4.
  • Rosén, Christoffer, 1986, et al. (författare)
  • Cerebrospinal fluid profiles of amyloid β-related biomarkers in Alzheimer's disease.
  • 2012
  • Ingår i: Neuromolecular medicine. - 1559-1174. ; 14:1, s. 65-73
  • Tidskriftsartikel (refereegranskat)abstract
    • The amyloid cascade hypothesis on the pathogenesis of Alzheimer's disease (AD) states that amyloid β (Aβ) accumulation in the brain is a key factor that initiates the neurodegenerative process. Aβ is generated from amyloid precursor protein (APP) through sequential cleavages by BACE1 (the major β-secretase in the brain) and γ-secretase. The purpose of this study was to characterize APP metabolism in vivo in AD patients versus cognitively healthy subjects by examining alterations in cerebrospinal fluid (CSF) biomarkers. We measured BACE1 activity and concentrations of α- and β-cleaved soluble APP (sAPPα and sAPPβ, respectively) and Aβ40 in CSF, biomarkers that all reflect the metabolism of APP, in 75 AD patients and 65 cognitively healthy controls. These analytes were also applied in a multivariate model to determine whether they provided any added diagnostic value to the core CSF AD biomarkers Aβ42, T-tau, and P-tau. We found no significant differences in BACE1 activity or sAPPα, sAPPβ, and Aβ40 concentrations between AD patients and controls. A multivariate model created with all analytes did not improve the separation of AD patients from controls compared with using the core AD biomarkers alone, highlighting the strong diagnostic performance of Aβ42, T-tau, and P-tau for AD. However, AD patients in advanced clinical stage, as determined by low MMSE score (≤20), had lower BACE1 activity and sAPPα, sAPPβ, and Aβ40 concentrations than patients with higher MMSE score, suggesting that these markers may be related to the severity of the disease.
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5.
  • Rosén, C., et al. (författare)
  • Discriminatory analysis of biochip-derived protein patterns in CSF and plasma in neurodegenerative diseases
  • 2011
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers. - 1663-4365. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of biomarkers in neurodegenerative diseases has been emphasized by recent research. Future clinical demands for identifying diseases at an early stage may render them essential. The aim of this pilot study was to test the analytical performance of two multiplex assays of cerebral markers on a well-defined clinical material consisting of patients with various neurodegenerative diseases. We measured 10 analytes in plasma and cerebrospinal fluid (CSF) from 60 patients suffering from Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, dementia with Lewy bodies, or mild cognitive impairment, as well as 20 cognitively healthy controls. We used the Randox biochip-based Evidence Investigator™ system to measure the analytes. We found it possible to measure most analytes in both plasma and CSF, and there were some interesting differences between the diagnostic groups, although with large overlaps. CSF heart-type fatty acid-binding protein was increased in AD. Glial fibrillary acidic protein and neutrophil gelatinase-associated lipocalin in CSF and D-dimer in plasma were elevated in patients with cerebrovascular disease. A multivariate statistical analysis revealed that the pattern of analytes could help to differentiate the conditions, although more studies are required to verify this.
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6.
  • Skillbäck, Tobias, et al. (författare)
  • Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia.
  • 2015
  • Ingår i: Brain : a journal of neurology. - : Oxford University Press. - 1460-2156. ; 138:Pt 9, s. 2716-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-β1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-β1-42 and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-β1-42 and amyloid-β1-42:phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-β1-42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-β1-42 was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with Lewy bodies and Parkinson's disease dementia groups 53%, 34%, 67% and 53% of the subjects, respectively had abnormal amyloid-β1-42 levels, 41%, 41%, 28% and 28% had abnormal total tau levels, and 29%, 28%, 25% and 19% had abnormal phosphorylated tau levels. Cerebrospinal fluid biomarkers were strongly associated with specific clinical dementia diagnoses with Alzheimer's disease and frontotemporal dementia showing the greatest difference in biomarker levels. In addition, cerebrospinal fluid amyloid-β1-42, total tau, phosphorylated tau and the amyloid-β1-42:phosphorylated tau ratio all correlated with poor cognitive performance in Alzheimer's disease, as did cerebrospinal fluid amyloid-β1-42 in Parkinson's disease dementia and vascular dementia. The results support the use of cerebrospinal fluid biomarkers to differentiate between dementias in clinical practice, and to estimate disease severity.
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7.
  • Olsson, Bob, 1969, et al. (författare)
  • CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.
  • 2016
  • Ingår i: The Lancet. Neurology. - 1474-4465. ; 15:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease (Aβ42, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF and blood to assess which of these were most altered in Alzheimer's disease.
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8.
  • Rosén, Christoffer, 1986, et al. (författare)
  • Alzheimer’s disease and other neurodegenerative disorders
  • 2015
  • Ingår i: Cerebrospinal Fluid in Clinical Neurology. - : Springer. - 9783319012254 ; , s. 329-351
  • Bokkapitel (refereegranskat)abstract
    • Traditionally, patients suffering from Alzheimer’s disease (AD) have been diagnosed according to clinical criteria, and a diagnosis has only been made in the dementia stage of the disease. Defi nite diagnosis required autopsy to confi rm the neuropathological fi ndings associated with AD, namely, extracellular depositions of amyloid a (Aa) protein and intraneuronal neurofi brillary tangles consisting of hyperphosphorylated tau (P-tau) protein, together with gross cortical atrophy caused by neuronal degeneration and loss. These fi ndings are refl ected in the cerebrospinal fl uid (CSF) of patients with AD. Numerous studies have shown that AD patients have lower levels of Aa42 and higher levels of P-tau and total tau (T-tau) in CSF than cognitively healthy controls. In the new diagnostic criteria for AD, these CSF biomarkers are included as in vivo evidence of AD neuropathology together with positron emission tomography (PET) measurements of global cortical amyloid load. Further, AD is now divided into several disease stages, namely, preclinical AD and mild cognitive impairment and dementia due to AD. In this chapter, we review CSF biomarker characteristics for the various disease stages for AD and how to use them in the differentiation against other common neurodegenerative disorders. New candidate CSF biomarkers for AD are also presented, as well as a discussion on the standardization of biomarkers and their application in clinical trials. © Springer International Publishing Switzerland 2015.
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9.
  • Rosén, Christoffer, 1986, et al. (författare)
  • Cerebrospinal fluid biomarkers for pathological processes in Alzheimer's disease
  • 2013
  • Ingår i: Current Opinion in Psychiatry. - 0951-7367. ; 26:3, s. 276-282
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose of review: To review the rationale behind and the use of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD). Established as well as new candidate biomarkers will be covered. Recent findings: AD is a complex disorder and the AD brain is characterized by multiple pathological processes, in addition to well-described plaque and tangle diseases. Recent studies have tried to address this by evaluating biomarkers related to features such as neuroinflammation, oxidative stress, microglial activation and synaptic degeneration, with some positive results. Summary: The CSF biomarkers total tau, phosphorylated-tau and the 42 amino acid isoform of amyloid beta reflect core elements of AD, that is, axonal degeneration, tangle disease and senile plaques, have been thoroughly tested and provide high diagnostic accuracy in the discrimination of patients with AD as compared with cognitively normal controls. They are also highly predictive of AD with dementia in patients with mild cognitive impairment, and have been included in new diagnostic criteria. New biomarkers may add to their diagnostic performance. Other potential fields of use include the monitoring of disease progression or pharmacodynamic drug effects. A common denominator for the candidate biomarkers is the need for validation in further studies to clarify their potential.
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10.
  • Rosén, Christoffer, 1986, et al. (författare)
  • Increased Levels of Chitotriosidase and YKL-40 in Cerebrospinal Fluid from Patients with Alzheimer's Disease.
  • 2014
  • Ingår i: Dementia and geriatric cognitive disorders extra. - 1664-5464. ; 4:2, s. 297-304
  • Tidskriftsartikel (refereegranskat)abstract
    • The cerebrospinal fluid (CSF) biomarkers total tau, abnormally phosphorylated tau and amyloid β 1-42 are strongly associated with Alzheimer's disease (AD). Apart from the pathologic hallmarks that these biomarkers represent, other processes such as inflammation and microglial activation are present in the brains of patients with AD. New biomarkers related to these processes could be valuable for the diagnosis and follow-up of AD patients and for the evaluation of inflammation-related pathologies.
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