| 1. |
- Vergallo, A., et al.
(författare)
-
Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers
- 2020
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 96, s. 22-32
-
Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation, a key early pathomechanistic alteration of Alzheimer's disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a longitudinal study in a monocentric cohort of cognitively healthy individuals at risk for Alzheimer's disease exploring whether age, sex, and the apolipoprotein E ε4 allele affect plasma YKL-40 concentrations. We investigated whether YKL-40 is associated with brain amyloid-β (Aβ) deposition, neuronal activity, and neurodegeneration as assessed via neuroimaging biomarkers. Finally, we investigated whether YKL-40 may predict cognitive performance. We found an age-associated increase of YKL-40 and observed that men display higher concentrations than women, indicating a potential sexual dimorphism. Moreover, YKL-40 was positively associated with memory performance and negatively associated with brain Aβ deposition (but not with metabolic signal). Consistent with translational studies, our results suggest a potentially protective effect of glia on incipient brain Aβ accumulation and neuronal homeostasis. © 2020 Elsevier Inc.
|
|
| 2. |
- Vergallo, A., et al.
(författare)
-
Plasma amyloid beta 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease
- 2019
-
Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:6, s. 764-775
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Blood-based biomarkers of pathophysiological brain amyloid beta (A beta) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the A beta(1-40)/A beta(1-42) ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain A beta positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-apriori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma A beta(1-40)/A beta(1-42) ratio. The accuracy is not affected by the apolipoprotein E (APOE) epsilon 4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma A beta(1-40)/A beta(1-42) ratio, assessed via Simoa, may improve future standard of care and clinical trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
|
|
| 3. |
- Simrén, Joel, 1996, et al.
(författare)
-
Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years
- 2022
-
Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:4
-
Tidskriftsartikel (refereegranskat)abstract
- The recent development of assays that accurately quantify neurofilament light, a neuronal cytoskeleton protein, in plasma has generated a vast literature supporting that it is a sensitive, dynamic, and robust biomarker of neuroaxonal damage. As a result, efforts are now made to introduce plasma neurofilament light into clinical routine practice, making it an easily accessible complement to its cerebrospinal fluid counterpart. An increasing literature supports the use of plasma neurofilament light in differentiating neurodegenerative diseases from their non-neurodegenerative mimics and suggests it is a valuable biomarker for the evaluation of the effect of putative disease-modifying treatments (e.g. in multiple sclerosis). More contexts of use will likely emerge over the coming years. However, to assist clinical interpretation of laboratory test values, it is crucial to establish normal reference intervals. In this study, we sought to derive reliable cut-offs by pooling quantified plasma neurofilament light in neurologically healthy participants (5-90 years) from eight cohorts. A strong relationship between age and plasma neurofilament light prompted us to define the following age-partitioned reference limits (upper 95(th) percentile in each age category): 5-17 years = 7 pg/mL; 18-50 years = 10 pg/mL; 51-60 years = 15 pg/mL; 61-70 years = 20 pg/mL; 70 + years = 35 pg/mL. The established reference limits across the lifespan will aid the introduction of plasma neurofilament light into clinical routine, and thereby contribute to diagnostics and disease-monitoring in neurological practice. Simren et al. report age-stratified cut-offs for plasma neurofilament light, based on a large material of healthy individuals across the ages 5-90 years. The findings will assist clinical implementation of plasma neurofilament light in clinical routine, by simplifying interpretation of concentrations across the lifespan as neurofilament light increases with age.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
