| 1. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 2. |
- Ehrenberg, Alexander J., et al.
(författare)
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Relevance of biomarkers across different neurodegenerative
- 2020
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Background: The panel of fluid- and imaging-based biomarkers available for neurodegenerative disease research is growing and has the potential to close important gaps in research and the clinic. With this growth and increasing use, appropriate implementation and interpretation are paramount. Various biomarkers feature nuanced differences in strengths, limitations, and biases that must be considered when investigating disease etiology and clinical utility. For example, neuropathological investigations of Alzheimer's disease pathogenesis can fall in disagreement with conclusions reached by biomarker-based investigations. Considering the varied strengths, limitations, and biases of different research methodologies and approaches may help harmonize disciplines within the neurodegenerative disease field. Purpose of review: Along with separate review articles covering fluid and imaging biomarkers in this issue of Alzheimer's Research and Therapy, we present the result of a discussion from the 2019 Biomarkers in Neurodegenerative Diseases course at the University College London. Here, we discuss themes of biomarker use in neurodegenerative disease research, commenting on appropriate use, interpretation, and considerations for implementation across different neurodegenerative diseases. We also draw attention to areas where biomarker use can be combined with other disciplines to understand issues of pathophysiology and etiology underlying dementia. Lastly, we highlight novel modalities that have been proposed in the landscape of neurodegenerative disease research and care.
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| 3. |
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| 4. |
- Hansson, Oskar, et al.
(författare)
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The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis : A review
- 2018
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:10, s. 1313-1333
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Cerebrospinal fluid (CSF) biomarkers have the potential to improve the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized preanalytical CSF handling protocols. Methods: This systematic review summarizes the current literature on the influence of preanalytical variables on CSF biomarker concentration. We evaluated the evidence for three core CSF biomarkers: β-amyloid 42, total tau, and phosphorylated tau. Results: The clinically important variables with the largest amount of conflicting data included the temperature at which samples are stored, the time nonfrozen samples can be stored, and possible effects of additives such as detergents, blood contamination, and centrifugation. Conversely, we discovered that there is consensus that tube material has a significant effect. Discussion: A unified CSF handling protocol is recommended to reduce preanalytical variability and facilitate comparison of CSF biomarkers across studies and laboratories. In future, experiments should use a gold standard with fresh CSF collected in low binding tubes.
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| 5. |
- Knopman, David S., et al.
(författare)
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The National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease : Perspectives from the Research Roundtable
- 2018
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:4, s. 563-575
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Forskningsöversikt (refereegranskat)abstract
- The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the “A, T, N System” (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed.
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| 6. |
- Leuzy, Antoine, et al.
(författare)
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Blood-based biomarkers for Alzheimer's disease
- 2022
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 14:1
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Forskningsöversikt (refereegranskat)abstract
- Neurodegenerative disorders such as Alzheimer's disease (AD) represent a mounting public health challenge. As these diseases are difficult to diagnose clinically, biomarkers of underlying pathophysiology are playing an ever-increasing role in research, clinical trials, and in the clinical work-up of patients. Though cerebrospinal fluid (CSF) and positron emission tomography (PET)-based measures are available, their use is not widespread due to limitations, including high costs and perceived invasiveness. As a result of rapid advances in the development of ultra-sensitive assays, the levels of pathological brain- and AD-related proteins can now be measured in blood, with recent work showing promising results. Plasma P-tau appears to be the best candidate marker during symptomatic AD (i.e., prodromal AD and AD dementia) and preclinical AD when combined with Aβ42/Aβ40. Though not AD-specific, blood NfL appears promising for the detection of neurodegeneration and could potentially be used to detect the effects of disease-modifying therapies. This review provides an overview of the progress achieved thus far using AD blood-based biomarkers, highlighting key areas of application and unmet challenges.
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| 7. |
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| 8. |
- Mattsson, Niklas, 1979
(författare)
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CSF biomarkers in neurodegenerative diseases.
- 2011
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Ingår i: Clinical chemistry and laboratory medicine : CCLM / FESCC. - 1434-6621. ; 49:3, s. 345-52
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Forskningsöversikt (refereegranskat)abstract
- Neurodegenerative diseases are major world wide causes of morbidity and mortality. They form a heterogeneous group of diseases, ranging from rare monogenic inherited errors of metabolism to common multi-factorial dementias. Major research efforts focus on the development of disease modifying drugs for neurodegenerative diseases. As a result, there follows a need for reliable tools for diagnosis, prognosis and monitoring of therapy. Processes in the brain can be monitored by analysis of cerebrospinal fluid (CSF). Several CSF biomarkers of pathological processes in the brain are now available. Such biomarkers may be used for both research and in the clinical setting. However, several difficult problems remain to be solved. More intensive collaboration between academia, industry and government is likely needed to develop treatments and biomarkers for neurodegenerative diseases. This article reviews the definitions, usage and current limitations of CSF biomarkers in this field.
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| 9. |
- Mattsson, Niklas, 1979, et al.
(författare)
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CSF biomarkers: pinpointing Alzheimer pathogenesis.
- 2009
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1180, s. 28-35
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Forskningsöversikt (refereegranskat)abstract
- Intense research during the last decades has resulted in an unprecedented accumulation of knowledge regarding the pathogenesis of Alzheimer's disease. Primarily, the focus has been directed toward amyloid and tau pathology and their relations to synaptic and neuronal loss. However, as the complexity of the disease becomes increasingly evident, the importance of other factors, such as inflammation, oxidative stress, and mitochondrial dysfunction, grow apparent. Here, we review available CSF biomarkers for these pathological processes. We also consider their usability in clinical practice and in clinical trials.
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| 10. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Future screening for incipient Alzheimer's disease--the influence of prevalence on test performance.
- 2009
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Ingår i: European neurology. - : S. Karger AG. - 1421-9913 .- 0014-3022. ; 62:4, s. 200-3
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Forskningsöversikt (refereegranskat)abstract
- Much effort has been made to identify and verify diagnostic biomarkers for early stage Alzheimer's disease (AD). The need for this is often advocated by possible future disease-modifying treatments, likely to be most effective if initiated early in the disease process. Since the neurodegenerative process probably starts many years before the first onset of symptoms, such future drugs are likely to invoke a need for screening presymptomatic individuals. Here, we speculate on the performance of currently available AD biomarkers in hypothetical screening programs of different designs. We note that many diagnostic tests will have an excellent ability to exclude upcoming AD. However, even the best tests will suffer from poor positive predictive values given the relatively low disease prevalence in populations with no or very few symptomatic individuals, also when taking future converters to AD into account. The magnitude of this problem, which is common among most screening programs, will depend on the efficacy, safety and cost of the future anti-AD drugs. A number of tentative solutions to the problem, apart from better tests, are discussed.
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