| 1. |
- Palmqvist, Sebastian, et al.
(författare)
-
Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease
- 2015
-
Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 85:14, s. 1240-1249
-
Tidskriftsartikel (refereegranskat)abstract
- Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF A42/t-tau and A42/p-tau performed better than CSF A42 and A42/40 (AUC difference 0.03-0.12, p < 0.05). Using nonoptimized cutoffs, CSF A42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.Conclusions:Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global A deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.Classification of evidence:This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.
|
|
| 2. |
- Andersson, Christin, et al.
(författare)
-
Increasing CSF phospho-tau levels during cognitive decline and progression to dementia
- 2008
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1466-1473
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression. OBJECTIVE: To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline. METHODS: Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM). RESULTS: There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up. CONCLUSION: Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
|
|
| 3. |
- Shahim, Pashtun, 1984, et al.
(författare)
-
Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury
- 2016
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 73:11, s. 1308-1315
-
Tidskriftsartikel (refereegranskat)abstract
- Importance:Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury.Objective:To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury.Design, Settings, and Participants:A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging.Main Outcomes and Measures:Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid β, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid.Results:A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (ρ = 0.58, P = .02 and ρ = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05).Conclusions and Relevance:Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy.
|
|
| 4. |
- Shahim, Pashtun, 1984, et al.
(författare)
-
Astroglial activation and altered amyloid metabolism in human repetitive concussion
- 2017
-
Ingår i: Neurology. - : American Academy of Neurology. - 0028-3878 .- 1526-632X. ; 88:15, s. 1400-1407
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood–brain barrier (BBB) impairment.Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25–12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Aβ38, Aβ40, Aβ42, sAPPα, and sAPPβ), and BBB function (CSF:serum albumin ratio).Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS >1 year. Athletes with PCS >1 year had higher RPQ scores and number of concussions than athletes with PCS <1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS >1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of Aβ40 and Aβ42 than controls. The CSF:serum albumin ratio was unaltered.Conclusions: This study suggests that PCS may be associated with biomarker evidence of astroglial activation and β-amyloid (Aβ) dysmetabolism in the brain. There was no clear evidence of Aβ deposition as Aβ40 and Aβ42 were reduced in parallel. The CSF:serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS.
|
|
| 5. |
- Schöll, Michael, 1980, et al.
(författare)
-
Biomarkers for tau pathology.
- 2019
-
Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 97, s. 18-33
-
Forskningsöversikt (refereegranskat)abstract
- The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions. Tau proteins have also been measured in blood, but the importance of tau-related changes in blood is still unclear. The recent addition of positron emission tomography ligands to visualize, map and quantify tau pathology has further contributed with information about the temporal and spatial characteristics of tau accumulation in the living brain. Together, the measurement of tau with fluid biomarkers and positron emission tomography constitutes the basis for a highly active field of research. This review describes the current state of biomarkers for tau biomarkers derived from neuroimaging and from the analysis of bodily fluids and their roles in the detection, diagnosis and prognosis of tau-associated neurodegenerative disorders, as well as their associations with neuropathological findings, and aims to provide a perspective on how these biomarkers might be employed prospectively in research and clinical settings.
|
|
| 6. |
- Janelidze, Shorena, et al.
(författare)
-
Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype
- 2017
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 104-112
-
Tidskriftsartikel (refereegranskat)abstract
- Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF bio-markers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage. (C) 2016 The Authors. Published by Elsevier Inc.
|
|
| 7. |
- Gard, Anna, et al.
(författare)
-
Quality of life of ice hockey players after retirement due to concussions
- 2020
-
Ingår i: Concussion. - : Future Medicine. - 2056-3299. ; 5:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sports-related concussion (SRC) is increasingly recognized as a potential health problem in ice hockey. Quality of life (QoL) in players retiring due to SRC has not been thoroughly addressed. Materials & methods: QoL using the Sports Concussion Assessment Tool 5th Edition, Impact of Event Scale-Revised and Short Form Health Survey was measured in Swedish ice hockey players who retired due to persistence of postconcussion symptoms or fear of attaining additional SRC. Results: A total of 76 players were assessed, on average of 5 years after their most recent SRC. Overall, retired players had a high burden of postconcussion symptoms and reduced QoL. Conclusion: Retired concussed ice hockey players have a reduced QoL, particularly those retiring due to postconcussion symptoms. Symptom burden should be continuously evaluated and guide the decision to retire.
|
|
| 8. |
- Millere, Elina, et al.
(författare)
-
Plasma neurofilament light chain as a potential biomarker in Charcot-Marie-Tooth disease.
- 2021
-
Ingår i: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 28:3, s. 974-981
-
Tidskriftsartikel (refereegranskat)abstract
- Charcot-Marie-Tooth (CMT) disease is a chronic, slowly progressing disorder. The lack of specific disease progression biomarkers limits the execution of clinical trials. However, neurofilament light chain (NfL) has been suggested as a potential biomarker for peripheral nervous system disorders.Ninety-six CMT disease patients and 60 healthy controls were enrolled in the study. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Blood plasma NfL concentrations were measured using the single-molecule array NfL assay.The NfL concentration was significantly higher in the CMT disease patient group than in the controls (p < 0.001). Of the CMT disease patients, those with type CMTX1 had a higher NfL level than those in the two other analysed subgroups (CMT1A and other CMT disease types) (p = 0.0498). The NfL concentration had a significant but weak correlation with the CMTNSv2 (rs = 0.25, p = 0.012). In one CMT disease patient with an extremely elevated NfL level, overlap with chronic inflammatory demyelinating polyneuropathy was suspected. Receiver operating characteristic analysis showed that an NfL concentration of 8.9 pg/ml could be used to discriminate CMT disease patients from controls, with an area under the curve of 0.881.Our study confirmed that the plasma NfL concentration is significantly higher in CMT disease patients than in controls. Plasma NfL concentration was found to significantly, albeit weakly, reflect the clinical severity of CMT disease. In the future, NfL may be used, either individually or collaboratively, as a biomarker in the clinical context of suspected CMT disease; however, several issues need to be addressed first.
|
|
| 9. |
- Samuelsson, Jessica, et al.
(författare)
-
A Western-style dietary pattern is associated with cerebrospinal fluid biomarker levels for preclinical Alzheimer's disease -A population-based cross-sectional study among 70-year-olds
- 2021
-
Ingår i: Alzheimer's & dementia (New York, N. Y.). - 2352-8737. ; 7:1, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Diet may be a modifiable factor for reducing the risk of Alzheimer's disease (AD). Western-style dietary patterns are considered to increase the risk, whereas Mediterranean-style dietary patterns are considered to reduce the risk. An association between diet and AD-related biomarkers have been suggested, but studies are limited.Aim: To investigate potential relations between dietary patterns and cerebrospinal fluid (CSF) biomarkers for AD among dementia-free older adults.Methods: Data were derived from the population-based Gothenburg H70 Birth Cohort Studies, Sweden. A total of 269 dementia-free 70-year-olds with dietary and cerebrospinal fluid (CSF) amyloid beta (Aβ42 and Aβ40), total tau (t-tau), and phosphorylated tau (p-tau) data were investigated. Dietary intake was determined by the diet history method, and four dietary patterns were derived by principal component analysis. A Western dietary pattern, a Mediterranean/prudent dietary pattern, a high-protein and alcohol pattern, and a high-total and saturated fat pattern. Logistic regression models, with CSF biomarker pathology (yes/no) as dependent variables, and linear regression models with continuous CSF biomarker levels as dependent variables were performed. The analyses were adjusted for sex, energy intake, body mass index (BMI), educational level, and physical activity level.Results: The odds ratio for having total tau pathology (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.02 to 2.01) and preclinical AD (Aβ42 and tau pathology; OR 1.79; 95% CI 1.03 to 3.10) was higher among those with a higher adherence to a Western dietary pattern. There were no other associations between the dietary patterns and CSF biomarkers that remained significant in both unadjusted and adjusted models.Discussion: Our findings suggest that higher adherence to a Western dietary pattern may be associated with pathological levels of AD biomarkers in the preclinical phase of AD. These findings can be added to the increasing amount of evidence linking diet with AD and may be useful for future intervention studies investigating dietary intake in relation to AD.
|
|
| 10. |
- von Otter, Malin, 1978, et al.
(författare)
-
Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract
- 2010
-
Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 131:2, s. 105-110
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and age-related cataract, disorders characterized by protein aggregation causing late-onset disease, both involve oxidative stress. We hypothesize that common variants of NFE2L2 and KEAP1, the genes encoding the main regulators of the Nrf2 system, an important defence system against oxidative stress, may influence risk of AD and/or age-related cataract. This case-control study combines an AD material (725 cases and 845 controls), and a cataract material (489 cases and 182 controls). Genetic variation in NFE2L2 and KEAP1 was tagged by eight and three tag single nucleotide polymorphisms (SNPs), respectively. Single SNPs and haplotypes were analyzed for associations with disease risk, age parameters, MMSE and AD cerebrospinal fluid biomarkers. NFE2L2 and KEAP1 were not associated with risk of AD or cataract. However, one haplotype allele of NFE2L2 was associated with 2 years earlier age at AD onset (pc 0.013) and 4 years earlier age at surgery for posterior subcapsular cataract (p(c) = 0.019). Another haplotype of NFE2L2 was associated with 4 years later age at surgery for cortical cataract (p(c) = 0.009). Our findings do not support NFE2L2 or KEAP1 as susceptibility genes for AD or cataract. However, common variants of the NFE2L2 gene may affect disease progression, potentially altering clinically recognized disease onset. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
|
|
