scholarly journals Cerebrospinal Fluid Aβ42/40 Corresponds Better than Aβ42 to Amyloid PET in Alzheimer’s Disease

2016 ◽  
Vol 55 (2) ◽  
pp. 813-822 ◽  
Author(s):  
Piotr Lewczuk ◽  
Anja Matzen ◽  
Kaj Blennow ◽  
Lucilla Parnetti ◽  
Jose Luis Molinuevo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Pet ◽  
Better Than

scholarly journals Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shorena Janelidze ◽  
Erik Stomrud ◽  
Ruben Smith ◽  
Sebastian Palmqvist ◽  
Niklas Mattsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Pet Tracer ◽  
Positron Emission ◽  
Diagnostic Work ◽  
Work Up ◽  
The Brain ◽  
Better Than

AbstractCerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.

Unravelling the Association Between Amyloid-PET and Cerebrospinal Fluid Biomarkers in the Alzheimer’s Disease Spectrum: Who Really Deserves an A+?

2021 ◽  
pp. 1-12
Author(s):  
Luca Sacchi ◽  
Tiziana Carandini ◽  
Giorgio Giulio Fumagalli ◽  
Anna Margherita Pietroboni ◽  
Valeria Elisa Contarino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Linear Regression Models ◽  
Csf Analysis ◽  
Disease Spectrum

Background: Association between cerebrospinal fluid (CSF)-amyloid-β (Aβ)42 and amyloid-PET measures is inconstant across the Alzheimer’s disease (AD) spectrum. However, they are considered interchangeable, along with Aβ 42/40 ratio, for defining ‘Alzheimer’s Disease pathologic change’ (A+). Objective: Herein, we further characterized the association between amyloid-PET and CSF biomarkers and tested their agreement in a cohort of AD spectrum patients. Methods: We include ed 23 patients who underwent amyloid-PET, MRI, and CSF analysis showing reduced levels of Aβ 42 within a 365-days interval. Thresholds used for dichotomization were: Aβ 42 <  640 pg/mL (Aβ 42+); pTau >  61 pg/mL (pTau+); and Aβ 42/40 <  0.069 (ADratio+). Amyloid-PET scans were visually assessed and processed by four pipelines (SPMCL, SPMAAL, FSGM, FSWC). Results: Different pipelines gave highly inter-correlated standardized uptake value ratios (SUVRs) (rho = 0.93–0.99). The most significant findings were: pTau positive correlation with SPMCL SUVR (rho = 0.56, p = 0.0063) and Aβ 42/40 negative correlation with SPMCL and SPMAAL SUVRs (rho = –0.56, p = 0.0058; rho = –0.52, p = 0.0117 respectively). No correlations between CSF-Aβ 42 and global SUVRs were observed. In subregion analysis, both pTau and Aβ 42/40 values significantly correlated with cingulate SUVRs from any pipeline (R2 = 0.55–0.59, p <  0.0083), with the strongest associations observed for the posterior/isthmus cingulate areas. However, only associations observed for Aβ 42/40 ratio were still significant in linear regression models. Moreover, combining pTau with Aβ 42 or using Aβ 42/40, instead of Aβ 42 alone, increased concordance with amyloid-PET status from 74% to 91% based on visual reads and from 78% to 96% based on Centiloids. Conclusion: We confirmed that, in the AD spectrum, amyloid-PET measures show a stronger association and a better agreement with CSF-Aβ 42/40 and secondarily pTau rather than Aβ 42 levels.

scholarly journals Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer’s disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria João Leitão ◽  
Anuschka Silva-Spínola ◽  
Isabel Santana ◽  
Veronica Olmedo ◽  
Alicia Nadal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Analytical Performance ◽  
Csf Biomarkers ◽  
Parameter Method ◽  
Routine Practice ◽  
Amyloid Pet ◽  
Β Amyloid ◽  
T Tau

Abstract Background Ongoing efforts within the Alzheimer’s disease (AD) field have focused on improving the intra- and inter-laboratory variability for cerebrospinal fluid (CSF) biomarkers. Fully automated assays offer the possibility to eliminate sample manipulation steps and are expected to contribute to this improvement. Recently, fully automated chemiluminescence enzyme immunoassays for the quantification of all four AD biomarkers in CSF became available. The aims of this study were to (i) evaluate the analytical performance of the Lumipulse G β-Amyloid 1-42 (restandardized to Certified Reference Materials), β-Amyloid 1-40, total Tau, and pTau 181 assays on the fully automated LUMIPULSE G600II; (ii) compare CSF biomarker results of the Lumipulse G assays with the established manual ELISA assays (INNOTEST®) from the same company (Fujirebio); and (iii) establish cut-off values and the clinical performance of the Lumipulse G assays for AD diagnosis. Methods Intra- and inter-assay variation was assessed in CSF samples with low, medium, and high concentrations of each parameter. Method comparison and clinical evaluation were performed on 40 neurological controls (NC) and 80 patients with a diagnosis of probable AD supported by a follow-up ≥ 3 years and/or positive amyloid PET imaging. A small validation cohort of 10 NC and 20 AD patients was also included to validate the cut-off values obtained on the training cohort. Results The maximal observed intra-assay and inter-assay coefficients of variation (CVs) were 3.25% and 5.50%, respectively. Method comparisons revealed correlation coefficients ranging from 0.89 (for Aβ40) to 0.98 (for t-Tau), with those for Aβ42 (0.93) and p-Tau (0.94) in-between. ROC curve analysis showed area under the curve values consistently above 0.85 for individual biomarkers other than Aβ40, and with the Aβ42/40, Aβ42/t-Tau, and Aβ42/p-Tau ratios outperforming Aβ42. Validation of the cut-off values in the independent cohort showed a sensitivity ranging from 75 to 95% and a specificity of 100%. The overall percentage of agreement between Lumipulse and INNOTEST was very high (> 87.5%). Conclusions The Lumipulse G assays show a very good analytical performance that makes them well-suited for CSF clinical routine measurements. The good clinical concordance between the Lumipulse G and INNOTEST assays facilitates the implementation of the new method in routine practice.

scholarly journals The Cerebrospinal Fluid Aβ1–42/Aβ1–40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer’s Disease in a Clinical Setting

2017 ◽  
Vol 60 (2) ◽  
pp. 561-576 ◽  
Author(s):  
Ellis Niemantsverdriet ◽  
Julie Ottoy ◽  
Charisse Somers ◽  
Ellen De Roeck ◽  
Hanne Struyfs ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Clinical Setting ◽  
Amyloid Pet

scholarly journals Clinical utility of Cerebrospinal Fluid Biomarkers for the Diagnosis of Alzheimer’s Disease in Korea

2020 ◽  
Author(s):  
Jongmin Lee ◽  
Hyemin Jang ◽  
Sung Hoon Kang ◽  
Jaeho Kim ◽  
Ji-Sun Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Clinical Utility ◽  
Medical Center ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Characteristic Analysis ◽  
Csf Biomarker ◽  
T Tau

Abstract Background Cerebrospinal fluid (CSF) biomarkers are increasingly used in clinical practice for the diagnosis of Alzheimer’s disease (AD). We aimed to 1) determine cutoff values of CSF biomarkers for AD, 2) investigate their clinical utility by estimating a concordance with amyloid positron emission tomography (PET), and 3) apply AT (amyloid/tau) classification based on CSF results. Methods We performed CSF analysis in 51 normal controls (NC), 23 amnestic mild cognitive impairment (aMCI) and 65 AD dementia (ADD) patients at the Samsung Medical Center in Korea. We tried to develop cutoff of CSF biomarkers for differentiating ADD from NC using receiver operating characteristic analysis. We also investigated a concordance between CSF and amyloid PET results and applied AT classification scheme based on CSF biomarker abnormalities to characterize our participants. Results CSF Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) significantly differ across the three groups. The area under curve for the differentiation between NC and ADD was highest in t-tau/Aβ42(0.994) followed by p-tau/Aβ42(0.963), Aβ42(0.960) and t-tau (0.918). The concordance rate between CSF Aβ42 and amyloid PET results was 92%. Finally, AT classification based on CSF biomarker abnormalities led to a majority of NC categorized into A-T-(72%), aMCI as A + T-(52%)/A + T+(30%), and AD as A + T+(56%)/A + T-(41%). Conclusion CSF biomarkers had high sensitivity and specificity in differentiating ADD from NC and were as accurate as amyloid PET. The AT group distribution was comparable to those of previous studies, which may serve to predict the prognosis more accurately than amyloid PET alone in the future.

scholarly journals Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

2020 ◽  
Author(s):  
Shorena Janelidze ◽  
Erik Stomrud ◽  
Ruben Smith ◽  
Sebastian Palmqvist ◽  
Niklas Mattsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Pet Tracer ◽  
Diagnostic Work ◽  
Work Up ◽  
The Brain ◽  
Diagnostic Work Up ◽  
Better Than

ABSTRACTCerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD) reflecting abnormal tau metabolism in the brain. Tau can be phosphorylated at multiple other sites including threonine 217, and here we investigated the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n=194), p-tau217 had stronger correlations with the tau PET tracer [18F]flortaucipir, and more accurately identified individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 were higher compared to p-tau181 and better correlated with [18F]flortaucipir retention. P-tau217 correlated better than p-tau181 with PET measures of neocortical amyloid-β burden and more accurately distinguished AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir were corroborated in an independent EXPEDITION3 trial cohort (n=32). These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.

Assessment of 18F-Florbetaben Amyloid PET Imaging in Patients with Suspected Alzheimer’s Disease and Isolated Increase in Cerebrospinal Fluid Tau Proteins

2019 ◽  
Vol 68 (3) ◽  
pp. 1061-1069 ◽  
Author(s):  
Chloé Manca ◽  
Lucie Hopes ◽  
Anna Kearney-Schwartz ◽  
Véronique Roch ◽  
Gilles Karcher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Pet Imaging ◽  
Tau Proteins ◽  
Amyloid Pet ◽  
Amyloid Pet Imaging

scholarly journals TDP-43 is elevated in plasma neuronal-derived exosomes of patients with Alzheimer's disease

2019 ◽  
Author(s):  
Nan Zhang ◽  
Dongmei Gu ◽  
Meng Meng ◽  
Marc L. Gordon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Oldest Old ◽  
Neuropsychiatric Symptoms ◽  
Apoe Genotype ◽  
Enzyme Linked Immunosorbent Assay ◽  
Amyloid Pet ◽  
Healthy Controls

Abstract Background Recently, TDP-43 has been recognized as a common proteinopathy in the “oldest old” and a neuropathological comorbidity in patients with Alzheimer’s disease (AD). However, since it has a low concentration in cerebrospinal fluid, the presence of TDP-43 in AD is rarely investigated in vivo. Methods Twenty-four patients with amyloid PET confirmed AD and 15 healthy controls (HCs) were included in this study. TDP-43 level in plasma neuronal-derived exosomes (NDEs) was measured by enzyme-linked immunosorbent assay. Results TDP-43 level was elevated in patients with AD compared with HCs (1.20 ± 0.91 ng/ml vs 0.64 ± 0.20 ng/ml, P < 0.039), after controlling for age. There was no correlation between TDP-43 level and cognitive function, neuropsychiatric symptoms or APOE genotype in patients with AD. Conclusions This study demonstrated increased TDP-43 accumulation in AD patients by examining plasma NDEs, which may provide a window into the effects of TDP-43 on AD progression.

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