| 1. |
- Chouraki, V, et al.
(författare)
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Plasma amyloid-β and risk of Alzheimer's disease in the Framingham Heart Study.
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Plasma amyloid-β (Aβ) peptide levels have been examined as a low-cost accessible marker for risk of incident Alzheimer's disease (AD) and dementia, but results have varied between studies. We reassessed these associations in one of the largest, prospective, community-based studies to date. METHODS: A total of 2189 dementia-free, Framingham Study participants aged >60 years (mean age, 72 ± 8 years; 56% women) had plasma Aβ1-42 and Aβ1-40 measured and were followed prospectively (mean, 7.6 ± 3.0 years) for dementia/AD. RESULTS: Increased plasma Aβ1-42 levels were associated with lower risk of dementia (Aβ1-42: hazard ratio [HR] = 0.80 [0.71‒0.90], P < .001; Aβ1-42-to-Aβ1-40 ratio: HR = 0.86 [0.76‒0.98], P = .027) and AD (Aβ1-42: HR = 0.79 [0.69‒0.90], P < .001; Aβ1-42-to-Aβ1-40 ratio: HR = 0.83 [0.72‒0.96], P = .012). CONCLUSION: Our results suggest that lower plasma Aβ levels are associated with risk of incident AD and dementia. They encourage further evaluation of plasma Aβ levels as a biomarker for risk of developing clinical AD and dementia. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 2. |
- Hansson, Oskar, et al.
(författare)
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Cerebral hypoperfusion is not associated with an increase in amyloid β pathology in middle-aged or elderly people
- 2018
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 14:1, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: It is hypothesized that cerebral hypoperfusion promotes the development of Alzheimer pathology. We therefore studied whether longstanding cerebral hypoperfusion is associated with Alzheimer pathology in nondemented humans.METHODS: Cerebral blood flow and amyloid β ((18)F-Flutemetamol) positron emission tomography retention were assessed in eleven patients with unilateral occlusion of precerebral arteries resulting in chronic and uneven hypoperfusion. A subset of patients underwent tau ((18)F-AV-1451) positron emission tomography.RESULTS: The blood flow was significantly reduced on the affected side of the brain in patients with unilateral occlusion of the internal carotid artery or stenosis of the middle cerebral artery. However, the cortical uptake of (18)F-Flutemetamol or (18)F-AV-1451 was not altered.DISCUSSION: Our results suggest that longstanding cerebral hypoperfusion in humans does not result in accumulation of amyloid β fibrils or tau aggregates.
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| 3. |
- Hansson, Oskar, et al.
(författare)
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CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression : A study of fully automated immunoassays in BioFINDER and ADNI cohorts
- 2018
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:11, s. 1470-1481
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. Methods: Cutoffs for Elecsys amyloid-β1–42 (Aβ), total tau/Aβ(1–42), and phosphorylated tau/Aβ(1–42) were defined against [18F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied. Results: CSF total tau/Aβ(1–42) and phosphorylated tau/Aβ(1–42) ratios were highly concordant with PET classification in BioFINDER (overall percent agreement: 90%; area under the curve: 94%). The CSF biomarker statuses established by predefined cutoffs were highly concordant with PET classification in Alzheimer's Disease Neuroimaging Initiative (overall percent agreement: 89%–90%; area under the curves: 96%) and predicted greater 2-year clinical decline in patients with mild cognitive impairment. Strikingly, tau/Aβ ratios were as accurate as semiquantitative PET image assessment in predicting visual read–based outcomes. Discussion: Elecsys CSF biomarker assays may provide reliable alternatives to PET in Alzheimer's disease diagnosis.
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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. |
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| 6. |
- Mattsson, Niklas, et al.
(författare)
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Predicting diagnosis and cognition with 18F-AV-1451 tau PET and structural MRI in Alzheimer's disease
- 2019
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:4, s. 570-580
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The relative importance of structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) to predict diagnosis and cognition in Alzheimer's disease (AD) is unclear. Methods: We tested 56 cognitively unimpaired controls (including 27 preclinical AD), 32 patients with prodromal AD, and 39 patients with AD dementia. Optimal classifiers were constructed using the least absolute shrinkage and selection operator with 18F-AV-1451 (tau) PET and structural MRI data (regional cortical thickness and subcortical volumes). Results: 18F-AV-1451 in the amygdala, entorhinal cortex, parahippocampal gyrus, fusiform, and inferior parietal lobule had 93% diagnostic accuracy for AD (prodromal or dementia). The MRI classifier involved partly the same regions plus the hippocampus, with 83% accuracy, but did not improve upon the tau classifier. 18F-AV-1451 retention and MRI were independently associated with cognition. Discussion: Optimized tau PET classifiers may diagnose AD with high accuracy, but both tau PET and structural brain MRI capture partly unique information relevant for the clinical deterioration in AD.
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| 7. |
- Mattsson, Niklas, et al.
(författare)
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Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
- 2018
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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| 8. |
- Palmqvist, Sebastian, et al.
(författare)
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Accurate risk estimation of β-amyloid positivity to identify prodromal Alzheimer's disease : Cross-validation study of practical algorithms
- 2019
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:2, s. 194-204
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim was to create readily available algorithms that estimate the individual risk of β-amyloid (Aβ) positivity. Methods: The algorithms were tested in BioFINDER (n = 391, subjective cognitive decline or mild cognitive impairment) and validated in Alzheimer's Disease Neuroimaging Initiative (n = 661, subjective cognitive decline or mild cognitive impairment). The examined predictors of Aβ status were demographics; cognitive tests; white matter lesions; apolipoprotein E (APOE); and plasma Aβ42/Aβ40, tau, and neurofilament light. Results: Aβ status was accurately estimated in BioFINDER using age, 10-word delayed recall or Mini–Mental State Examination, and APOE (area under the receiver operating characteristics curve = 0.81 [0.77–0.85] to 0.83 [0.79–0.87]). When validated, the models performed almost identical in Alzheimer's Disease Neuroimaging Initiative (area under the receiver operating characteristics curve = 0.80–0.82) and within different age, subjective cognitive decline, and mild cognitive impairment populations. Plasma Aβ42/Aβ40 improved the models slightly. Discussion: The algorithms are implemented on http://amyloidrisk.com where the individual probability of being Aβ positive can be calculated. This is useful in the workup of prodromal Alzheimer's disease and can reduce the number needed to screen in Alzheimer's disease trials.
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| 9. |
- Smith, Ruben, et al.
(författare)
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18F-AV1451 pet detects tau pathology in mapt mutation carriers and correlates strongly with immunohistochemistry of tau aggregates
- 2016
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 12:7 Suppl, s. 723-724
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Konferensbidrag (refereegranskat)abstract
- Background: The Tau PET ligand 18F-AV1451 has been shown to reliably detect paired helical filaments of tau in Alzheimer's disease, but it is not yet known whether it binds to the tau aggregates present in patients with mutations in the gene (MAPT) coding for the tau protein. Further, no study has yet compared the cerebral retention of 18F -AV1451 with the tau aggregates revealed using neuropathology. Methods: Three patients from a Swedish family carrying the R406W mutation of MAPT were assessed with cognitive tests and subjects underwent 18F-AV1451 and 18F-Flutemetamol PET scans. Further one of younger subjects also underwent an 18F-FDG PET scan. The oldest subject died two weeks after the scan and the brain was processed for neuropathology. Tau immunohistochemistry was performed on brain sections from affected and unaffected brain regions. Results: Two mutation carriers, aged 56 and 60 years, had disease durations of 5-10 years and still only exhibited mild-moderate episodic memory impairment and no clear behavioural deficits. The MRI revealed only slight cortical atrophy and 18F-AV1451 PET imaging showed uptake in the hippocampus and the temporal lobes, especially in the inferior and anterior parts (Fig 1A, B). The uptake of 18F - AV1451 correlated well with hypometabolism revealed with FGD PET in one of the subjects. The third case, 76 years, had a disease duration of ≥20 years and exhibited clear cognitive impairment, behavioural disturbances, mutism and dysphagia. The CT scan showed generalised cortical atrophy with a pronounced temporal lobe atrophy and 18F -AV1451 PET imaging revealed uptake in the temporal and frontal lobes, as well as in the basal ganglia (Fig 1 C). The regional uptake of 18F -AV1451 correlated strongly with the tau aggregates revealed using immunohistochemistry (R2 = 0.80, P <0.01; Fig 2). All cases exhibited negative amyloid (18F -flutemetamol) PET scans. Conclusions: The in vivo uptake of 18F-AV1451 reflects the regional amount of tau aggregates revealed by neuropathological examination. Further, tau pathology in MAPT mutation carriers is accurately detected with 18F -AV1451 PET, which consequently can be used to track the effects of anti-tau therapies in this patient group. (Figure Presented) .
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