| 1. |
- Dittrich, Anna, 1972, et al.
(författare)
-
Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration: The H70 Birth Cohort Study in Gothenburg.
- 2023
-
Ingår i: Neurology. - 1526-632X. ; 101:3
-
Tidskriftsartikel (refereegranskat)abstract
- Studies associate chronic kidney disease (CKD) with neurodegeneration. This study investigated the relationship between kidney function, blood, CSF, and structural brain MRI markers of neurodegeneration in a sample including individuals with and without CKD.Participants from the Gothenburg H70 Birth Cohort Study, with data on plasma neurofilament light (P-NfL), estimated glomerular filtration rate (eGFR), and structural brain MRI were included. Participants were invited to also have the CSF collected. The primary endpoint of this study was to determine any association between CKD and P-NfL. Secondary endpoints included cross-sectional associations between CKD, eGFR, and CSF-derived and MRI-derived markers of neurodegeneration and Alzheimer disease (AD) pathology (MRI: cortical thickness, hippocampal volume, lateral ventricle volume, and white matter lesion volume; CSF: β-amyloid (Aβ) 42, Aβ42/40, Aβ42/p-tau, t-tau, p-tau, and NfL). Participants with P-NfL and eGFR at baseline were re-examined on eGFR, 5.5 (5.3-6.1) years (median; IQR) after the first visit, and the predictive value of P-NfL levels on incident CKD was estimated longitudinally, using a Cox proportional hazards model.We included 744 participants, 668 without CKD (age 71 [70-71] years, 50% males) and 76 with CKD (age 71 [70-71] years, 39% males). Biomarkers from the CSF were analyzed in 313 participants. A total of 558 individuals returned for a re-examination of eGFR (75% response rate, age 76 [76; 77] years, 48% males, 76 new cases of CKD). Participants with CKD had higher P-NfL levels than those with normal kidney function (median; 18.8 vs 14.1 pg/mL, p < 0.001), while MRI and CSF markers were similar between the groups. P-NfL was independently associated with CKD after adjustment for confounding variables, including hypertension and diabetes (OR; 3.231, p < 0.001), in a logistic regression model. eGFR and CSF Aβ 42/40: R = 0.23, p = 0.004 correlated in participants with Aβ42 pathology. P-NfL levels in the highest quartile were associated with incident CKD at follow-up (HR; 2.39 [1.21: 4.72]).In a community-based cohort of 70-year olds, P-NfL was associated with both prevalent and incident CKD, while CSF and/or imaging measures did not differ by CKD status. Participants with CKD and dementia presented similar levels of P-NfL.
|
|
| 2. |
- Dittrich, Anna, 1972, et al.
(författare)
-
Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community-based sample of 70-year-olds
- 2022
-
Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light protein (NfL) in cerebrospinal fluid (CSF) and plasma (P) are suggested to be interchangeable markers of neurodegeneration. However, evidence is scarce from community-based samples. NfL was examined in a small-scale sample of 287 individuals from the Gothenburg H70 Birth cohort 1944 study, using linear models in relation to CSF and magnetic resonance imaging (MRI) biomarker evidence of neurodegeneration. CSF-NfL and P-NfL present distinct associations with biomarker evidence of Alzheimer's disease (AD) pathology and neurodegeneration. P-NfL was associated with several markers that are characteristic of AD, including smaller hippocampal volumes, amyloid beta (A beta)(42), A beta(42/40), and A beta(42)/t-tau (total tau). CSF-NfL demonstrated associations with measures of synaptic and neurodegeneration, including t-tau, phosphorylated tau (p-tau), and neurogranin. Our findings suggest that P-NfL and CSF-NfL may exert different effects on markers of neurodegeneration in a small-scale community-based sample of 70-year-olds.
|
|
| 3. |
- Dittrich, Anna, 1972, et al.
(författare)
-
Proportion of Community-Dwelling Individuals Older Than 70 Years Eligible for Lecanemab Initiation: The Gothenburg H70 Birth Cohort Study.
- 2024
-
Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 102:9
-
Tidskriftsartikel (refereegranskat)abstract
- To determine the prevalence of individuals with Alzheimer disease (AD) eligible for treatment with the recently FDA-approved lecanemab based on data from a population-based sample of 70-year-olds and extrapolate an estimation of individuals eligible in Europe and the United States.Participants from the Gothenburg H70 Birth Cohort Study with clinical data, CSF-amyloid beta 42, and brain MRI analysis were evaluated for eligibility to receive lecanemab treatment according to FDA-approved recommendations, noting factors requiring special consideration. Results were used to extrapolate the number of eligible individuals in Europe and the United States using public demographic data.Thirty (10.3%) of 290 participants met the indication for treatment of whom 18 (6.2%) were eligible and did not present factors requiring special consideration. Our estimate that 6.2% of all 70-year-olds in the full cohort are eligible for treatment extrapolates to an approximation that around 5.9 million Europeans and 2.2 million US residents could be eligible.Information on proportion of individuals eligible for AD treatment with lecanemab in the general public is limited. We provide information on 70-year-olds in Sweden and extrapolate these data to Europe and the United States. This study opens for larger studies on this proportion and implementation of lecanemab treatment.
|
|
| 4. |
- Meda, Francisco J, 1997, et al.
(författare)
-
Neurofilament light oligomers in neurodegenerative diseases: quantification by homogeneous immunoassay in cerebrospinal fluid
- 2023
-
Ingår i: BMJ NEUROLOGY OPEN. - : BMJ. - 2632-6140. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Neurofilament light (NfL) is a widely used biomarker for neurodegeneration. NfL is prone to oligomerisation, but available assays do not reveal the exact molecular nature of the protein variant measured. The objective of this study was to develop a homogeneous ELISA capable of quantifying oligomeric NfL (oNfL) in cerebrospinal fluid (CSF). Methods A homogeneous ELISA, based on the same capture and detection antibody (NfL21), was developed and used to quantify oNfL in samples from patients with behavioural variant frontotemporal dementia (bvFTD, n=28), non-fluent variant primary progressive aphasia (nfvPPA, n=23), semantic variant PPA (svPPA, n=10), Alzheimer's disease (AD, n=20) and healthy controls (n=20). The nature of NfL in CSF, and the recombinant protein calibrator, was also characterised by size exclusion chromatography (SEC). Results CSF concentration of oNfL was significantly higher in nfvPPA (p<0.0001) and svPPA patients (p<0.05) compared with controls. CSF oNfL concentration was also significantly higher in nfvPPA compared with bvFTD (p<0.001) and AD (p<0.01) patients. SEC data showed a peak fraction compatible with a full-length dimer (similar to 135 kDa) in the in-house calibrator. For CSF, the peak was found in a fraction of lower molecular weight (similar to 53 kDa), suggesting dimerisation of NfL fragments. Conclusions The homogeneous ELISA and SEC data suggest that most of the NfL in both the calibrator and human CSF is present as a dimer. In CSF, the dimer appears to be truncated. Further studies are needed to determine its precise molecular composition.
|
|
