Diagnostic performance of a fully automated chemiluminescent enzyme immunoassay for Alzheimer's disease diagnosis

Paciotti, Silvia; Sepe, Federica Nicoletta; Farotti, Lucia; Cataldi, Samuela; Gatticchi, Leonardo; Parnetti, Lucilla

doi:10.1016/j.cca.2019.03.1612

Cited by 22 publications

(32 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The wide availability of automated platforms represents an important achievement for reducing the pre-analytical variability of core AD biomarker assays in routine clinical setting [20]. With respect to classical manual ELISAs, automated platforms give us also the possibility to measure single samples and to obtain the results within approximately 30 minutes, allowing clinicians to provide urgent diagnoses in very short time.…”

Section: Discussionmentioning

confidence: 99%

“…The standardization of preanalytical and analytical procedures (i.e., freeze/thaw cycles [11], CSF storage volumes [11], pipettetips and tube materials [12,13], storage temperature [14] and variability due to the operator [15]) represents a crucial factor in biomarker assays [10]. In this context, automated [16][17][18][19][20] and semiautomated [21] platforms may play a major role in minimizing inter-laboratory differences in biomarker assays. Fully automated chemiluminescent platforms [20], showed high sensitivity and specificity for early diagnosis of AD, with an optimal concordance with manual ELISA assays [18,20] and amyloid-targeted Positron Emission Tomography (PET) [19,22].…”

Section: Introductionmentioning

confidence: 99%

“…In this context, automated [16][17][18][19][20] and semiautomated [21] platforms may play a major role in minimizing inter-laboratory differences in biomarker assays. Fully automated chemiluminescent platforms [20], showed high sensitivity and specificity for early diagnosis of AD, with an optimal concordance with manual ELISA assays [18,20] and amyloid-targeted Positron Emission Tomography (PET) [19,22]. Moreover, these platforms offer the possibility to easily and quickly analyze any single and fresh CSF samples, a feature that could be useful when a timely response is needed by clinicians.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Bellomo

Cataldi

Paciotti

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: cerebrospinal fluid (CSF) amyloid-beta (Aβ) 42/40 ratio, threonine-181phosphorylated-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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Bellomo

Cataldi

Paciotti

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The following cutoff values for abnormal CSF biomarkers were employed: ratio CSF Aβ 1-42 /Aβ 1-40 < 0.10, phospho-tau 181 > 40 pg/ml, and total tau > 456 pg/ml, as measured using Lumipulse G Assays (Fujirebio, Malvern, PA) on the LUMIPULSE G fully automated platform (Bayart et al, 2019;Paciotti et al, 2019). CSF samples from all three cohorts were measured all together in one day by trained operators who were blinded to the clinical information.…”

Section: Measurement Of Ad Csf Core Biomarkersmentioning

confidence: 99%

CSF sTREM2 correlates with CSF tau in advancing Parkinson’s disease

Wilson

Swarovski

Linortner

et al. 2019

Preprint

View full text Add to dashboard Cite

222 Introduction: 565 Participants and Methods: 966 Abstract Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD) and affects 1% of the population above 60 years old. Although PD commonly manifests with motor symptoms, a majority of patients with PD subsequently develop cognitive impairment which often progresses to dementia, a major cause of morbidity and disability. PD is characterized by α -synuclein accumulation that frequently associates with amyloid beta (Aβ) and tau fibrils, the hallmarks of AD neuropathologic changes; this cooccurrence suggests that onset of cognitive decline in PD may be associated with appearance of pathologic Aβ and/or tau. Recent studies have highlighted the appearance of the soluble form of the Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) receptor in CSF during development of AD. Given the known association of microglial activation with advancing PD, we investigated whether CSF and/or plasma sTREM2 increased with progression to PD dementia. We examined 165 participants consisting of 17 cognitively normal elderly, 45 PD patients with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF Aβ and tau levels revealed that CSF sTREM2concentrations were elevated in PD subgroups with abnormal tau, but not Aβ, CSF concentration. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in PD that is associated with cognitive decline.

show abstract

“…The standardization of pre-analytical and analytical procedures (i.e., freeze/thaw cycles [11], CSF storage volumes [11], pipette-tips and tube materials [12,13], storage temperature [14] and variability due to the operator [15]) represents a crucial factor in biomarker assays [10]. In this context, automated [16][17][18][19][20] and semi-automated [21] platforms may play a major role in minimizing inter-laboratory differences in biomarker assays. Fully automated chemiluminescent platforms [20], showed high sensitivity and speci city for early diagnosis of AD, with an optimal concordance with manual ELISA assays [18,20] and amyloid-targeted Positron Emission Tomography (PET) [19,22].…”

Section: Introductionmentioning

confidence: 99%

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

Bellomo

Cataldi

Paciotti

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Diagnostic performance of a fully automated chemiluminescent enzyme immunoassay for Alzheimer's disease diagnosis

Cited by 22 publications

References 16 publications

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

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

CSF sTREM2 correlates with CSF tau in advancing Parkinson’s disease

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

Contact Info

Product

Resources

About