scholarly journals Measurement of CSF core Alzheimer Disease biomarkers for routine clinical diagnosis: do fresh vs frozen samples differ?

2020 ◽  
Author(s):  
Giovanni Bellomo ◽  
Samuela Cataldi ◽  
Silvia Paciotti ◽  
Federico Paolini Paoletti ◽  
Davide Chiasserini ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Disease Biomarkers ◽  
Total Tau ◽  
N Classification ◽  
Significant Achievement ◽  
Lower Variability ◽  
Automated Platform ◽  
Diagnostic Work ◽  
Relative Differences ◽  
T Tau

Abstract Background: cerebrospinal fluid (CSF) amyloid-beta (Aβ) 42/40 ratio, threonine-181-phosphorylated-tau (p-tau) and total-tau (t-tau) represent core biomarkers of Alzheimer Disease (AD). The recent availability of automated platforms has represented a significant achievement for reducing the pre-analytical variability of these determinations in clinical setting. With respect to classical manual ELISAs, these platforms give us also the possibility to measure any single sample and to get the result within approximately 30 min. So far, reference values have been calculated from measurements obtained in frozen samples. In this work, we wanted to check if the values obtained in fresh CSF samples differ from those obtained in frozen samples, since this issue is mandatory in routine diagnostic work.Methods: fifty-eight consecutive CSF samples have been analyzed immediately after lumbar puncture and after one-month deep freezing (-80°C). As automated platform we used Lumipulse G600-II (Fujirebio Inc.). Both the fresh and the frozen aliquots were analyzed in their storage tubes.Results: in fresh samples, a mean increase of Aβ40 (6%), Aβ42 (2%), p-tau (2%) and t-tau (4%) was observed as compared to frozen samples, whereas a slight decrease was observed for Aβ42/Aβ40 ratio (4%), due to the higher deviation of Aβ40 in fresh samples compared to Aβ42.These differences are significant for Aβ40, Aβ42/Aβ40 ratio, p-tau and t-tau. Nevertheless, Aβ42/Aβ40 ratio showed a lower variability (smaller standard deviation of relative differences) with respect to Aβ42. With respect to the AD profile according to the A/T/(N) criteria for AD diagnosis, no significant changes in classification were observed when comparing results obtained in fresh vs frozen samples.Conclusions: small but significant differences have been found for Aβ40, Aβ42/Aβ40 ratio, p-tau and t-tau in fresh vs frozen samples. Importantly, these differences did not imply a modification in the A/T/(N) classification system. In order to know if different cut-offs for fresh and frozen samples are required, larger, multi-center investigations are needed.

scholarly journals Measurement of CSF core Alzheimer Disease biomarkers for routine clinical diagnosis: do fresh vs frozen samples differ?

2020 ◽  
Author(s):  
Giovanni Bellomo ◽  
Samuela Cataldi ◽  
Silvia Paciotti ◽  
Federico Paolini Paoletti ◽  
Davide Chiasserini ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Disease Biomarkers ◽  
Total Tau ◽  
N Classification ◽  
Significant Achievement ◽  
Lower Variability ◽  
Automated Platform ◽  
Diagnostic Work ◽  
Relative Differences ◽  
T Tau

Abstract Background: cerebrospinal fluid (CSF) amyloid-beta (Aβ) 42/40 ratio, threonine-181-phosphorylated-tau (p-tau) and total-tau (t-tau) represent core biomarkers of Alzheimer Disease (AD). The recent availability of automated platforms has represented a significant achievement for reducing the pre-analytical variability of these determinations in clinical setting. With respect to classical manual ELISAs, these platforms give us also the possibility to measure any single sample and to get the result within approximately 30 min. So far, reference values have been calculated from measurements obtained in frozen samples. In this work, we wanted to check if the values obtained in fresh CSF samples differ from those obtained in frozen samples, since this issue is mandatory in routine diagnostic work.Methods: fifty-eight consecutive CSF samples have been analyzed immediately after lumbar puncture and after one-month deep freezing (-80°C). As automated platform we used Lumipulse G600-II (Fujirebio Inc.). Both the fresh and the frozen aliquots were analyzed in their storage tubes. Results: in fresh samples, a mean increase of Aβ40 (6%), Aβ42 (2%), p-tau (2%) and t-tau (4%) was observed as compared to frozen samples, whereas a slight decrease was observed for Aβ42/Aβ40 ratio (4%), due to the higher deviation of Aβ40 in fresh samples compared to Aβ42.These differences are significant for Aβ40, Aβ42/Aβ40 ratio, p-tau and t-tau. Nevertheless, Aβ42/Aβ40 ratio showed a lower variability (smaller standard deviation of relative differences) with respect to Aβ42. With respect to the AD profile according to the A/T/(N) criteria for AD diagnosis, no significant changes in classification were observed when comparing results obtained in fresh vs frozen samples. Conclusions: small but significant differences have been found for Aβ40, Aβ42/Aβ40 ratio, p-tau and t-tau in fresh vs frozen samples. Importantly, these differences did not imply a modification in the A/T/(N) classification system. In order to know if different cut-offs for fresh and frozen samples are required, larger, multi-center investigations are needed.

scholarly journals Measurement of CSF core Alzheimer disease biomarkers for routine clinical diagnosis: do fresh vs frozen samples differ?

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Giovanni Bellomo ◽  
Samuela Cataldi ◽  
Silvia Paciotti ◽  
Federico Paolini Paoletti ◽  
Davide Chiasserini ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Disease Biomarkers ◽  
Total Tau ◽  
N Classification ◽  
Significant Achievement ◽  
Lower Variability ◽  
Automated Platform ◽  
Diagnostic Work ◽  
Relative Differences ◽  
T Tau

Abstract Background Cerebrospinal fluid (CSF) amyloid-beta (Aβ) 42/40 ratio, threonine-181-phosphorylated-tau (p-tau), and total-tau (t-tau) represent core biomarkers of Alzheimer disease (AD). The recent availability of automated platforms has represented a significant achievement for reducing the pre-analytical variability of these determinations in clinical setting. With respect to classical manual ELISAs, these platforms give us also the possibility to measure any single sample and to get the result within approximately 30 min. So far, reference values have been calculated from measurements obtained in frozen samples. In this work, we wanted to check if the values obtained in fresh CSF samples differ from those obtained in frozen samples, since this issue is mandatory in routine diagnostic work. Methods Fifty-eight consecutive CSF samples have been analyzed immediately after lumbar puncture and after 1-month deep freezing (− 80 °C). As an automated platform, we used Lumipulse G600-II (Fujirebio Inc.). Both the fresh and the frozen aliquots were analyzed in their storage tubes. Results In fresh samples, a mean increase of Aβ40 (6%), Aβ42 (2%), p-tau (2%), and t-tau (4%) was observed as compared to frozen samples, whereas a slight decrease was observed for Aβ42/Aβ40 ratio (4%), due to the higher deviation of Aβ40 in fresh samples compared to Aβ42. These differences are significant for Aβ40, Aβ42/Aβ40 ratio, p-tau, and t-tau. Nevertheless, the Aβ42/Aβ40 ratio showed a lower variability (smaller standard deviation of relative differences) with respect to Aβ42. With respect to the AD profile according to the A/T/(N) criteria for AD diagnosis, no significant changes in classification were observed when comparing results obtained in fresh vs frozen samples. Conclusions Small but significant differences have been found for Aβ40, Aβ42/Aβ40 ratio, p-tau, and t-tau in fresh vs frozen samples. Importantly, these differences did not imply a modification in the A/T/(N) classification system. In order to know if different cutoffs for fresh and frozen samples are required, larger, multi-center investigations are needed.

scholarly journals Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults

Neurology ◽  
2017 ◽  
Vol 89 (12) ◽  
pp. 1251-1255 ◽  
Author(s):  
Ge Li ◽  
Cynthia L. Mayer ◽  
Daniel Morelli ◽  
Steven P. Millard ◽  
Wendy H. Raskind ◽  
...  
Keyword(s):  
Treatment Group ◽  
Alzheimer Disease ◽  
Density Lipoprotein ◽  
Analysis Of Covariance ◽  
Cognitively Normal ◽  
Treatment Groups ◽  
Disease Biomarkers ◽  
Total Tau ◽  
Disease Modifying ◽  
Normal Adults

Objective:To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure.Methods:Participants were 45–64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group). Simvastatin was titrated to 40 mg/d. CSF Aβ42, total tau, and p-tau181 were measured at baseline and after 12 months of treatment using the INNO-BIA AlzBio3 assay. We used analysis of covariance to assess differences in biomarker change from baseline between treatment groups, adjusting for age, sex, and APOE ε4 status.Results:Changes from baseline did not differ significantly between treatment groups for any CSF biomarker, with p values of 0.53, 0.36, and 0.25 for CSF Aβ42, total tau, and p-tau181, respectively. There was no significant modifying effect of sex, APOE ε4, or baseline high-density lipoprotein or triglycerides on treatment group for any of the biomarkers (all p > 0.18). However, a significant interaction between treatment group and baseline low-density lipoprotein (LDL) was observed for p-tau181 (p = 0.003), where greater decreases from baseline in CSF p-tau181 concentrations were associated with higher baseline LDL level for the simvastatin group.Conclusions:Simvastatin-related reductions in CSF p-tau181 concentrations may be modulated by LDL cholesterol. The potential disease-modifying effects of simvastatin on CSF phospho-tau should be further investigated in persons with hypercholesterolemia.

scholarly journals Cognitively Normal APOE ε4 Carriers Have Specific Elevation of CSF SNAP-25

2020 ◽  
Author(s):  
Omar Hameed Butt ◽  
Justin M Long ◽  
Rachel L. Henson ◽  
Elizabeth Herries ◽  
Courtney L. Sutphen ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Genetic Risk ◽  
Carrier Status ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Cognitively Normal ◽  
Disease Research ◽  
Total Tau ◽  
T Tau ◽  
Phosphorylated Tau 181

Abstract Background: Cerebrospinal fluid (CSF) synaptosomal-associated protein 25 (SNAP-25) and neurogranin are recently described biomarkers for synaptic integrity that are known to be elevated in the CSF of symptomatic Alzheimer disease (AD). Their relationship with Apolipoprotein E (APOE) ε4 carrier status, the major genetic risk factor for AD, remains unclear.Methods: In this study, CSF SNAP-25 and neurogranin were compared in cognitively normal APOE ε4 carriers and non-carriers (n=274, mean age 65.0 ± 9.0 years, 39% APOE ε4 carriers, 58% female) enrolled at the Knight Alzheimer Disease Research Center, and in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database.Results: SNAP-25, a biomarker of pre-synaptic integrity, was specifically elevated in APOE ε4 carriers versus non-carriers (5.95 ± 1.72 pg/ml, 4.44 ± 1.40 pg/ml, p <0.0001), even after adjusting for age, sex, years of education, and amyloid status (p <0.0001). In contrast, CSF neurogranin, a biomarker of post-synaptic integrity, did not vary by APOE ε4 status. Further, CSF total tau (t-tau), phosphorylated-tau-181 (ptau181), and neurofilament light chain (NfL) also did not vary by APOE ε4 status. Similar results were observed in the ADNI cohort. Conclusion: Our findings suggest APOE ε4 carriers have both amyloid-related and amyloid-independent presynaptic disruption as reflected by elevated CSF SNAP-25 levels. In contrast, post-synaptic disruption as reflected by elevations in CSF neurogranin is related to amyloid status.

scholarly journals Lipid Peroxidation Assessment in Preclinical Alzheimer Disease Diagnosis

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1043
Author(s):  
Carmen Peña-Bautista ◽  
Lourdes Álvarez-Sánchez ◽  
Inés Ferrer ◽  
Marina López-Nogueroles ◽  
Antonio José Cañada-Martínez ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Area Under Curve ◽  
Disease Diagnosis ◽  
Csf Biomarkers ◽  
Preclinical Ad ◽  
Aging Populations ◽  
Advanced Stages ◽  
Preclinical Diagnosis ◽  
T Tau ◽  
And Oxidative Stress

Background: Alzheimer disease (AD) is an increasingly common neurodegenerative disease, especially in countries with aging populations. Its diagnosis is complex and is usually carried out in advanced stages of the disease. In addition, lipids and oxidative stress have been related to AD since the earliest stages. A diagnosis in the initial or preclinical stages of the disease could help in a more effective action of the treatments. Methods: Isoprostanoid biomarkers were determined in plasma samples from preclinical AD participants (n = 12) and healthy controls (n = 31) by chromatography and mass spectrometry (UPLC-MS/MS). Participants were accurately classified according to cerebrospinal fluid (CSF) biomarkers and neuropsychological examination. Results: Isoprostanoid levels did not show differences between groups. However, some of them correlated with CSF biomarkers (t-tau, p-tau) and with cognitive decline. In addition, a panel including 10 biomarkers showed an area under curve (AUC) of 0.96 (0.903–1) and a validation AUC of 0.90 in preclinical AD prediction. Conclusions: Plasma isoprostanoids could be useful biomarkers in preclinical diagnosis for AD. However, these results would require a further validation with an external cohort.

scholarly journals Episodic memory and speed/attention deficits are associated with Alzheimer-typical CSF abnormalities in MCI

2008 ◽  
Vol 14 (4) ◽  
pp. 582-590 ◽  
Author(s):  
ARTO NORDLUND ◽  
SINDRE ROLSTAD ◽  
OLA KLANG ◽  
KARIN LIND ◽  
MONA PEDERSEN ◽  
...  
Keyword(s):  
Episodic Memory ◽  
Neuropsychological Battery ◽  
Prodromal Stage ◽  
Age Norms ◽  
Total Tau ◽  
Prodromal Ad ◽  
Function Language ◽  
T Tau ◽  
Normal Controls ◽  
Better Than

Mild cognitive impairment (MCI) is regarded as the prodromal stage of dementia disorders, such as Alzheimer's disease (AD).Objective: To compare the neuropsychological profiles of MCI subjects with normal concentrations of total tau (T-τ) and Aβ42 in CSF (MCI-norm) to MCI subjects with deviating concentrations of the biomarkers (MCI-dev). MCI-norm (N = 73) and MCI-dev (N = 73) subjects were compared to normal controls (N = 50) on tests of speed/attention, memory, visuospatial function, language and executive function.Results: MCI-norm performed overall better than MCI-dev, specifically on tests of speed and attention and episodic memory. When MCI-dev subjects were subclassified into those with only high T-tau (MCI-tau), only low Aβ42 (MCI-Aβ) and both high T-tau and low Aβ42 (MCI-tauAβ), MCI-tauAβ tended to perform slightly worse. MCI-tau and MCI-Aβ performed quite similarly.Conclusions: Considering the neuropsychological differences, many MCI-norm probably had more benign forms of MCI, or early non-AD forms of neurodegenerative disorders. Although most MCI-dev performed clearly worse than MCI-norm on the neuropsychological battery, some did not show any deficits when compared to age norms. A combination of CSF analyses and neuropsychology could be a step toward a more exact diagnosis of MCI as prodromal AD. (JINS, 2008, 14, 582–590.)

scholarly journals A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers

Neurology ◽  
2016 ◽  
Vol 87 (5) ◽  
pp. 539-547 ◽  
Author(s):  
Clifford R. Jack ◽  
David A. Bennett ◽  
Kaj Blennow ◽  
Maria C. Carrillo ◽  
Howard H. Feldman ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Classification Scheme ◽  
Disease Biomarkers

P3-319: DEPRESSION AND ALZHEIMER DISEASE BIOMARKERS PREDICT DRIVING DECLINE

2006 ◽  
Vol 14 (7S_Part_22) ◽  
pp. P1202-P1203
Author(s):  
Ganesh M. Babulal ◽  
Suzie Chen ◽  
Monique M. Williams ◽  
Jean-Francois Trani ◽  
Parul Bakhshi ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Disease Biomarkers

scholarly journals Comparison of GOME-2/MetOp total ozone data with Brewer spectroradiometer data over the Iberian Peninsula

2009 ◽  
Vol 27 (4) ◽  
pp. 1377-1386 ◽  
Author(s):  
M. Antón ◽  
D. Loyola ◽  
M. López ◽  
J. M. Vilaplana ◽  
M. Bañón ◽  
...  
Keyword(s):  
Iberian Peninsula ◽  
Total Ozone ◽  
A Priori ◽  
Retrieval Algorithm ◽  
Data Dependencies ◽  
Ozone Data ◽  
Significant Dependence ◽  
Ozone Profile ◽  
Lower Variability ◽  
Relative Differences

Abstract. The main objective of this article is to compare the total ozone data from the new Global Ozone Monitoring Experiment instrument (GOME-2/MetOp) with reliable ground-based measurement recorded by five Brewer spectroradiometers in the Iberian Peninsula. In addition, a similar comparison for the predecessor instrument GOME/ERS-2 is described. The period of study is a whole year from May 2007 to April 2008. The results show that GOME-2/MetOp ozone data already has a very good quality, total ozone columns are on average 3.05% lower than Brewer measurements. This underestimation is higher than that obtained for GOME/ERS-2 (1.46%). However, the relative differences between GOME-2/MetOp and Brewer measurements show significantly lower variability than the differences between GOME/ERS-2 and Brewer data. Dependencies of these relative differences with respect to the satellite solar zenith angle (SZA), the satellite scan angle, the satellite cloud cover fraction (CF), and the ground-based total ozone measurements are analyzed. For both GOME instruments, differences show no significant dependence on SZA. However, GOME-2/MetOp data show a significant dependence on the satellite scan angle (+1.5%). In addition, GOME/ERS-2 differences present a clear dependence with respect to the CF and ground-based total ozone; such differences are minimized for GOME-2/MetOp. The comparison between the daily total ozone values provided by both GOME instruments shows that GOME-2/MetOp ozone data are on average 1.46% lower than GOME/ERS-2 data without any seasonal dependence. Finally, deviations of a priori climatological ozone profile used by the satellite retrieval algorithm from the true ozone profile are analyzed. Although excellent agreement between a priori climatological and measured partial ozone values is found for the middle and high stratosphere, relative differences greater than 15% are common for the troposphere and lower stratosphere.

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