| 1. |
- Ashton, Nicholas J., et al.
(författare)
-
A multicentre validation study of the diagnostic value of plasma neurofilament light
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
|
|
| 2. |
- Benedet, Andréa L., et al.
(författare)
-
Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals
- 2019
-
Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 11, s. 679-689
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Methods: Voxelwise regression models tested the cross-sectional association between [18F]fluorodeoxyglucose ([18F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [18F]FDG in amyloid positive (Aβ+) and negative (Aβ−) subjects. Results: Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [18F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [18F]FDG-NfL were confined to cognitively impaired Aβ+ individuals. Discussion: These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.
|
|
| 3. |
- Ferreira, Pamela C. L., et al.
(författare)
-
Endocannabinoid System Biomarkers in Alzheimer's Disease
- 2023
-
Ingår i: CANNABIS AND CANNABINOID RESEARCH. - : Mary Ann Liebert Inc. - 2578-5125 .- 2378-8763. ; 8:1, s. 77-91
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alterations in the endocannabinoid system (ES) have been described in Alzheimer's disease (AD) pathophysiology. In the past years, multiple ES biomarkers have been developed, promising to advance our understanding of ES changes in AD.Discussion: ES biomarkers, including positron emission tomography with cannabinoid receptors tracers and biofluid-based endocannabinoids, are associated with AD disease progression and pathological features.Conclusion: Although not specific enough for AD diagnosis, ES biomarkers hold promise for prognosis, drug-target engagement, and a better understanding of the disease. Here, we summarize currently available ES biomarker findings and discuss their potential applications in the AD research field.
|
|
| 4. |
- Lessa Benedet, Andréa, et al.
(författare)
-
Stage-specific links between plasma neurofilament light and imaging biomarkers of Alzheimer's disease
- 2020
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:12, s. 3793-3804
-
Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light (NfL) is a marker of neuroaxonal injury, a prominent feature of Alzheimer's disease. It remains uncertain, however, how it relates to amyloid and tau pathology or neurodegeneration across the Alzheimer's disease continuum. The aim of this study was to investigate how plasma NfL relates to amyloid and tau PET and MRI measures of brain atrophy in participants with and without cognitive impairment. We retrospectively examined the association between plasma NfL and MRI measures of grey/white matter volumes in the Alzheimer's Disease Neuroimaging Initiative [ADNI: n = 1149; 382 cognitively unimpaired control subjects and 767 cognitively impaired participants (mild cognitive impairment n = 420, Alzheimer's disease dementia n = 347)]. Longitudinal plasma NfL was measured using single molecule array (Simoa) technology. Cross-sectional associations between plasma NfL and PET amyloid and tau measures were independently assessed in two cohorts: ADNI [n = 198; 110 cognitively unimpaired, 88 cognitively impaired (MCI n = 67, Alzheimer's disease dementia n = 21), data accessed October 2018]; and Translational Biomarkers in Aging and Dementia [TRIAD, n = 116; 74 cognitively unimpaired, 42 cognitively impaired (MCI n = 16, Alzheimer's disease dementia n = 26), data obtained November 2017 to January 2019]. Associations between plasma NfL and imaging-derived measures were examined voxel-wise using linear regression (cross-sectional) and linear mixed effect models (longitudinal). Cross-sectional analyses in both cohorts showed that plasma NfL was associated with PET findings in brain regions typically affected by Alzheimer's disease; associations were specific to amyloid PET in cognitively unimpaired and tau PET in cognitively impaired (P < 0.05). Longitudinal analyses showed that NfL levels were associated with grey/white matter volume loss; grey matter atrophy in cognitively unimpaired was specific to APOE ϵ4 carriers (P < 0.05). These findings suggest that plasma NfL increases in response to amyloid-related neuronal injury in preclinical stages of Alzheimer's disease, but is related to tau-mediated neurodegeneration in symptomatic patients. As such, plasma NfL may a useful measure to monitor effects in disease-modifying drug trials.
|
|
| 5. |
- Leuzy, Antoine, et al.
(författare)
-
A multicenter comparison of [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis
- 2021
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:7, s. 2295-2305
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aims to determine whether comparable target regions of interest (ROIs) and cut-offs can be used across [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau positron emission tomography (PET) tracers for differential diagnosis of Alzheimer’s disease (AD) dementia vs either cognitively unimpaired (CU) individuals or non-AD neurodegenerative diseases. Methods: A total of 1755 participants underwent tau PET using either [18F]flortaucipir (n = 975), [18F]RO948 (n = 493), or [18F]MK6240 (n = 287). SUVR values were calculated across four theory-driven ROIs and several tracer-specific data-driven (hierarchical clustering) regions of interest (ROIs). Diagnostic performance and cut-offs for ROIs were determined using receiver operating characteristic analyses and the Youden index, respectively. Results: Comparable diagnostic performance (area under the receiver operating characteristic curve [AUC]) was observed between theory- and data-driven ROIs. The theory-defined temporal meta-ROI generally performed very well for all three tracers (AUCs: 0.926–0.996). An SUVR value of approximately 1.35 was a common threshold when using this ROI. Conclusion: The temporal meta-ROI can be used for differential diagnosis of dementia patients with [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET with high accuracy, and that using very similar cut-offs of around 1.35 SUVR. This ROI/SUVR cut-off can also be applied across tracers to define tau positivity.
|
|
| 6. |
- Pascoal, Tharick A., et al.
(författare)
-
Discriminative accuracy of the A/T/N scheme to identify cognitive impairment due to Alzheimer's disease
- 2023
-
Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The optimal combination of amyloid-β/tau/neurodegeneration (A/T/N) biomarker profiles for the diagnosis of Alzheimer's disease (AD) dementia is unclear. Methods: We examined the discriminative accuracy of A/T/N combinations assessed with neuroimaging biomarkers for the differentiation of AD from cognitively unimpaired (CU) elderly and non-AD neurodegenerative diseases in the TRIAD, BioFINDER-1 and BioFINDER-2 cohorts (total n = 832) using area under the receiver operating characteristic curves (AUC). Results: For the diagnosis of AD dementia (vs. CU elderly), T biomarkers performed as well as the complete A/T/N system (AUC range: 0.90–0.99). A and T biomarkers in isolation performed as well as the complete A/T/N system in differentiating AD dementia from non-AD neurodegenerative diseases (AUC range; A biomarker: 0.84–1; T biomarker: 0.83–1). Discussion: In diagnostic settings, the use of A or T neuroimaging biomarkers alone can reduce patient burden and medical costs compared with using their combination, without significantly compromising accuracy.
|
|
