| 11. |
- Keshavan, A., et al.
(författare)
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Concordance of csf measures of alzheimer’s pathology with amyloid pet status in a preclinical cohort: A comparison of lumipulse and established immunoassays
- 2021
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with presymptomatic Alzheimer’s disease (AD) pathology on amyloid positron emission tomography (PET). METHODS: In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays and inter-platform Pearson correlations derived. Lumipulse Aβ42 measures were adjusted to incorporate standardization to certified reference materials. Logistic regressions and receiver operating characteristics analysis generated CSF cut-points optimizing concordance with18F florbetapir amyloid PET status (n = 63). RESULTS: Measurements of CSF Aβ, p-tau181, and their ratios correlated well across platforms (r 0.84 to 0.94, P < .0001); those of t-tau and t-tau/Aβ42 correlated moderately (r 0.57 to 0.79, P < .0001). The best concordance with amyloid PET (100% sensitivity and 94% specificity) was afforded by cut-points of 0.075 for Lumipulse Aβ42/Aβ40, 0.087 for MSD Aβ42/Aβ40 and 17.3 for Lumipulse Aβ42/p-tau181. DISCUSSION: The Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre-symptomatic AD pathology. © 2020 The Authors.
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| 12. |
- Ma, Y., et al.
(författare)
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Measurement batch differences and between-batch conversion of Alzheimer's disease cerebrospinal fluid biomarker values
- 2021
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Batch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods. Methods A total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker ratios. Batch differences were assessed using Bland-Altman plot, paired t test, Pitman-Morgan test, and linear regression. Generalized linear models were applied to convert CSF values between batches. Results We found statistically significant batch differences for all biomarkers and ratios, except that neurofilament light was comparable between batches 1 and 2. The conversion models generally had high R-2 except for converting P-tau between batches 1 and 3. Discussion Between-batch conversion allows harmonized CSF values to be used in the same analysis. Such method may be applied to adjust for other sources of variability in measuring CSF or other types of biomarkers.
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| 13. |
- Najar, Jenna, et al.
(författare)
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Polygenic risk scores for Alzheimer's disease are related to dementia risk in APOE ɛ4 negatives.
- 2021
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Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Studies examining the effect of polygenic risk scores (PRS) for Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype on incident dementia in very old individuals are lacking.A population-based sample of 2052 individuals ages 70 to 111, from Sweden, was followed in relation to dementia. AD-PRSs including 39, 57, 1333, and 13,942 single nucleotide polymorphisms (SNPs) were used.AD-PRSs (including 39 or 57 SNPs) were associated with dementia (57-SNPs AD-PRS: hazard ratio 1.09, confidence interval 1.01-1.19, P=.03), particularly in APOE ɛ4 non-carriers (57-SNPs AD-PRS: 1.15, 1.05-1.27, P=4 × 10-3, 39-SNPs AD-PRS: 1.22, 1.10-1.35, P=2 × 10-4). No association was found with the other AD-PRSs. Further, APOE ɛ4 was associated with increased risk of dementia (1.60, 1.35-1.92, P=1 × 10-7). In those aged ≥95 years, the results were similar for the AD-PRSs, while APOE ɛ4 only predicted dementia in the low-risk tertile of AD-PRSs.These results provide information to identify individuals at increased risk of dementia.
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| 14. |
- Nilsson, Johanna, 1993, et al.
(författare)
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Cerebrospinal fluid biomarker panel for synaptic dysfunction in Alzheimer's disease
- 2021
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Synaptic dysfunction and degeneration is one of the earliest events in Alzheimer's disease (AD) and the best correlate of cognitive decline. Thus, identification and validation of biomarkers reflecting synaptic degeneration to be used as prognostic biomarkers are greatly needed. Method Solid-phase extraction and parallel reaction monitoring mass spectrometry were used to quantify 17 synaptic proteins in CSF, in two cross-sectional studies including AD (n = 52) and controls (n = 37). Results Increased concentrations of beta-synuclein, gamma-synuclein, neurogranin, phosphatidylethanolamine-binding protein 1, and 14-3-3 proteins were observed in AD patients compared to controls, while neuronal pentraxin-2 and neuronal pentraxin receptor were decreased. Discussion We have established a method with a novel panel of synaptic proteins as biomarkers of synaptic dysfunction. The results indicate that several of the proteins included in the panel may serve as synaptic biomarkers for AD.
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| 15. |
- Pannee, Josef, 1979, et al.
(författare)
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The global Alzheimer's Association round robin study on plasma amyloid beta methods
- 2021
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Blood-based assays to measure brain amyloid beta (A beta) deposition are an attractive alternative to the cerebrospinal fluid (CSF)-based assays currently used in clinical settings. In this study, we examined different blood-based assays to measure A beta and how they compare among centers and assays. Methods Aliquots from 81 plasma samples were distributed to 10 participating centers. Seven immunological assays and four mass-spectrometric methods were used to measure plasma A beta concentrations. Results Correlations were weak for A beta 42 while A beta 40 correlations were stronger. The ratio A beta 42/A beta 40 did not improve the correlations and showed weak correlations. Discussion The poor correlations for A beta 42 in plasma might have several potential explanations, such as the high levels of plasma proteins (compared to CSF), sensitivity to pre-analytical sample handling and specificity, and cross-reactivity of different antibodies. Different methods might also measure different pools of plasma A beta 42. We, however, hypothesize that greater correlations might be seen in future studies because many of the methods have been refined during completion of this study.
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| 16. |
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| 17. |
- Sannemann, Lena, et al.
(författare)
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General practitioners’ attitude toward early and pre-dementia diagnosis of ad in five European countries—a mopead project survey
- 2021
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: General practitioners (GPs) play a key role in early identification of dementia, yet diagnosis is often missed or delayed in primary care. As part of the multinational Models of Patient Engagement for Alzheimer’s Disease project, we assess GPs’ attitude toward early and pre-dementia diagnosis of AD and explore barriers to early diagnosis. Methods: Our survey covered general attitude toward early diagnosis, diagnostic procedures, resources, and opinion on present and future treatment options across five European countries. Results: In total 343 GPs completed the survey; 74% of GPs indicated that an early diagnosis is valuable. There were country-specific differences in GPs’ perceptions of reimbursement and time available for the patient. If a drug were available to slow down the progression of AD, 59% of the GPs would change their implementation of early diagnosis. Discussion: Our findings provide insight into GPs’ attitudes by exploring differences in perception and management of early diagnosis.
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| 18. |
- Simrén, Joel, 1996, et al.
(författare)
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Blood neurofilament light in remote settings: Alternative protocols to support sample collection in challenging pre-analytical conditions.
- 2021
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Ingår i: Alzheimer's & dementia. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated alternative pre-analytical handling of blood for neurofilament light (NfL) analysis where resources are limited.Plasma NfL was measured with single molecule array after alternative blood processing procedures: dried plasma spots (DPS), dried blood spots (DBS), and delayed 48-hour centrifugation. These were compared to standardized plasma processing (reference standard [RS]). In a discovery cohort (n=10) and a confirmatory cohort (n=21), whole blood was obtained from individuals with unknown clinical etiology. In the confirmatory cohort, delayed centrifugation protocol was paired with either 37°C incubation or sample shaking to test the effect of these parameters.Delayed centrifugation (R2=0.991) and DPS (discovery cohort, R2=0.954; confirmatory cohort, DPS: R2=0.961) methods were strongly associated with the RS. Delayed centrifugation with higher temperatures (R2=0.995) and shaking (R2=0.975) did not affect this association. DPS (P<0.001) returned concentrations considerably lower than the RS.DPS or delayed centrifugation are viable pre-analytical procedures for the accurate quantification of plasma NfL.
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| 19. |
- Skillbäck, Tobias, et al.
(författare)
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Sex differences in CSF biomarkers for neurodegeneration and blood-brain barrier integrity.
- 2021
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Ingår i: Alzheimer's & dementia. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the CSF/serum albumin ratio (QAlb) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand.Participants were derived from two Swedish samples: the population-based H70 Study (n = 308, age 70) and a clinical routine cohort (CSF NfL, n = 8995, QAlb, n = 39252, age 0 to 95). In the population-based study, QAlb and NfL were examined in relation to sex, cardiovascular risk factors, and cerebral white matter lesions (WMLs). In the clinical cohort, QAlb and NfL sex differences were tested in relation to age.Men had higher QAlb and NfL concentrations and had higher QAlb and NfL concentrations from adolescence throughout life. NfL was not related to WML, but QAlb correlated positively with WMLs.The CSF NfL sex difference could not be explained by vascular pathology. Future studies should consider using different reference limits for men and women.
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| 20. |
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