| 1. |
- Bjerke, Maria, 1977, et al.
(författare)
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Assessing the commutability of reference material formats for the harmonization of amyloid beta measurements.
- 2016
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Ingår i: Clinical chemistry and laboratory medicine : CCLM / FESCC. - : Walter de Gruyter GmbH. - 1437-4331 .- 1434-6621. ; 54:7, s. 1177-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cerebrospinal fluid (CSF) amyloid-β (Aβ42) peptide is an important biomarker for Alzheimer's disease (AD). Variability in measured Aβ42 concentrations at different laboratories may be overcome by standardization and establishing traceability to a reference system. Candidate certified reference materials (CRMs) are validated herein for this purpose. METHODS: Commutability of 16 candidate CRM formats was assessed across five CSF Aβ42 immunoassays and one mass spectrometry (MS) method in a set of 48 individual clinical CSF samples. Promising candidate CRM formats (neat CSF and CSF spiked with Aβ42) were identified and subjected to validation across eight (Elecsys, EUROIMMUN, IBL, INNO-BIA AlzBio3, INNOTEST, MSD, Simoa, and Saladax) immunoassays and the MS method in 32 individual CSF samples. Commutability was evaluated by Passing-Bablok regression and the candidate CRM termed commutable when found within the prediction interval (PI). The relative distance to the regression line was assessed. RESULTS: The neat CSF candidate CRM format was commutable for almost all method comparisons, except for the Simoa/MSD, Simoa/MS and MS/IBL where it was found just outside the 95% PI. However, the neat CSF was found within 5% relative distance to the regression line for MS/IBL, between 5% and 10% for Simoa/MS and between 10% and 15% for Simoa/MSD comparisons. CONCLUSIONS: The neat CSF candidate CRM format was commutable for 33 of 36 method comparisons, only one comparison more than expected given the 95% PI acceptance limit. We conclude that the neat CSF candidate CRM can be used for value assignment of the kit calibrators for the different Aβ42 methods.
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| 2. |
- Sandelius, Anna Stina, 1952, et al.
(författare)
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Transient increase in CSF GAP-43 concentration after ischemic stroke.
- 2018
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers reflect ongoing processes in the brain. Growth-associated protein 43 (GAP-43) is highly upregulated in brain tissue shortly after experimental ischemia suggesting the CSF GAP-43 concentration may be altered in ischemic brain disorders. CSF GAP-43 concentration is elevated in Alzheimer's disease patients; however, patients suffering from stroke have not been studied previously.The concentration of GAP-43 was measured in longitudinal CSF samples from 28 stroke patients prospectively collected on days 0-1, 2-4, 7-9, 3 weeks, and 3-5 months after ischemia and cross-sectionally in 19 controls. The stroke patients were clinically evaluated using a stroke severity score system. The extent of the brain lesion, including injury size and degrees of white matter lesions and atrophy were evaluated by CT and magnetic resonance imaging.Increased GAP-43 concentration was detected from day 7-9 to 3 weeks after stroke, compared to day 1-4 and to levels in the control group (P = 0.02 and P = 0.007). At 3-5 months after stroke GAP-43 returned to admission levels. The initial increase in GAP-43 during the nine first days was associated to stroke severity, the degree of white matter lesions and atrophy and correlated positively with infarct size (rs = 0.65, P = 0.001).The transient increase of CSF GAP-43 is important to take into account when used as a biomarker for other neurodegenerative diseases such as Alzheimer's disease. Furthermore, GAP-43 may be a marker of neuronal responses after stroke and additional studies confirming the potential of CSF GAP-43 to reflect severity and outcome of stroke in larger cohorts are warranted.
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| 3. |
- Sandelius, Åsa P, et al.
(författare)
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Cerebrospinal fluid growth-associated protein 43 in multiple sclerosis.
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegeneration in multiple sclerosis (MS) correlates with disease progression and reparative processes may be triggered. Growth-associated protein 43 (GAP-43) exhibits induced expression during axonal growth and reduced expression during MS progression. We aimed to evaluate if GAP-43 can serve as a biomarker of regeneration in relapsing-remitting MS (RRMS) and whether disease-modifying therapies (DMTs) influence GAP-43 concentration in cerebrospinal fluid (CSF). GAP-43 was measured using an enzyme-linked immunosorbent assay in 105 MS patients (73 RRMS, 12 primary progressive MS, 20 secondary progressive MS) and 23 healthy controls (HCs). In 35 of the patients, lumbar puncture, clinical assessment, and magnetic resonance imaging was performed before initiation of therapeutic intervention, and at follow-up. CSF GAP-43 concentration was significantly lower in progressive MS compared with HCs (p = 0.004) and RRMS (p = < 0.001) and correlated negatively with disability (p = 0.026). However, DMTs did not alter CSF GAP-43. Interestingly, in RRMS CSF GAP-43 levels were higher in patients with signs of active inflammatory disease than in patients in remission (p = 0.042). According to CSF GAP-43 concentrations, regeneration seems reduced in progressive MS, increased during disease activity in RRMS but is unaffected by treatment of highly active DMTs.
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| 4. |
- Sandelius, Åsa P, et al.
(författare)
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Elevated CSF GAP-43 is Alzheimer's disease specific and associated with tau and amyloid pathology.
- 2019
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 15:1, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- The level of the presynaptic protein growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) has previously been shown to be increased in Alzheimer's disease (AD) and thus may serve as an outcome measure in clinical trials and facilitate earlier disease detection.We developed an enzyme-linked immunosorbent assay for CSF GAP-43 and measured healthy controls (n = 43), patients with AD (n = 275), or patients with other neurodegenerative diseases (n = 344). In a subpopulation (n = 93), CSF GAP-43 concentrations from neuropathologically confirmed cases were related to Aβ plaques, tau, α-synuclein, and TDP-43 pathologies.GAP-43 was significantly increased in AD compared to controls and most neurodegenerative diseases and correlated with the magnitude of neurofibrillary tangles and Aβ plaques in the hippocampus, amygdala, and cortex. GAP-43 was not associated to α-synuclein or TDP-43 pathology.The presynaptic marker GAP-43 is associated with both diagnosis and neuropathology of AD and thus may be useful as a sensitive and specific biomarker for clinical research.
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