- Email: [email protected]
AMYLOID-PET CONCORDANCE OF ELECSYS® CSF BIOMARKER IMMUNOASSAYS FOR ALZHEIMER’S DISEASE
Podium Presentations: Sunday, July 16, 2017
time-period in which CSF Aß1-42 levels remained stable (20142015). Data-driven cut-points were determined with Gaussian mixture modelling based on raw and corrected CSF data, and diagnostic performance was assessed for each year. Results: Over 15 years time aß1-42 levels showed an upward drift, with a slope depending on diagnosis (pinteraction<.001; figure 1): SCD (beta¼28, SE¼3, p<.001), MCI subjects (beta¼26, SE¼3, p<.001) and dementia other (beta¼26, SE¼4, p<.001 ) showed steeper drifts than AD subjects (beta¼14, SE¼4, p<.001). Mixture-modelling based on drift-corrected and normalised data resulted in a cut-point of 749 pg/ml, providing a stable average sensitivity of 93% (variability over time 4%), which is comparable (p>.05) to a mixture-modelling based cut-point of 680 pg/ml from raw data (92% sensitivity; variability over time 4%) and a more stable and improved specificity (p¼.01) of 86% (variability over time 10%) compared to raw data of 68% specificity, variability over time 24%. Conclusions: Drift effects in Aß1-42 CSF levels over time depend on diagnosis. Adjusting for drift effects in a diagnostic specific way improves and stabilises the specificity performance to distinguish AD from controls. O1-05-04
CLINICAL PERFORMANCE OF NEUROGRANIN AS A CEREBROSPINAL FLUID BIOMARKER FOR ALZHEIMER’S DISEASE: AN ASSAY COMPARISON STUDY
Eline AJ. Willemse1,2,3, Ann De Vos4, Elizabeth M. Herries5, Ulf Andreasson6, Sebastiaan Engelborghs7, Eugeen Vanmechelen8, Wiesje M. van der Flier9,10, Philip Scheltens11, Jack H. Ladenson5, Henrik Zetterberg12,13, Kaj Blennow14, Anne M. Fagan5, Maria Bjerke15, Charlotte E. Teunissen16, 1Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, Antwerp, Belgium; 2Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands; 3Neurochemistry Lab, Clinical Chemistry, VU University Medical Center, Amsterdam, Netherlands; 4ADx NeuroSciences, Ghent, Belgium; 5Washington University School of Medicine, St. Louis, MO, USA; 6Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; 7Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; 8ADx NeuroSciences, Gent, Belgium; 9Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands; 10Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands; 11Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands; 12Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; 13University College London, London, United Kingdom; 14Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, M€ olndal, Sweden; 15Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; 16Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: [email protected] Background: Neurogranin is a postsynaptic protein elevated in cere-
brospinal fluid (CSF) of Alzheimer’s disease (AD) patients. The correlation with cognitive decline evokes promise to use CSF Neurogranin to monitor disease progression. Current assays report divergent ranges of Neurogranin concentrations, and differ in which form of Neurogranin is being measured. This study compares the analytical and clinical performance of three commonly used Neurogranin assays in the same cohort of patients. Methods:
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Intra-assay and inter-assay CV, LLOD, calibrators of the other assays, and Neurogranin in brain lysate were measured in: Neurogranin immunoassay performed on an Erenna instrument from WashU (St.Louis, MO), Neurogranin ELISA from ADx NeuroSciences (Ghent, Belgium), and Neurogranin ELISA from UGot (Gothenburg, Sweden). 108 CSF samples from 22 controls with subjective cognitive decline, 22 AD, 22 frontotemporal dementia, 22 dementia with Lewy Bodies, and 20 vascular dementia were selected. Passing-Bablok regression was used to compare the three assays and Kruskal-Wallis was used for Neurogranin group comparisons. Calibrators and antibodies of the three immunoassays were also tested for their reciprocal affinities on Western blot. Results: All immunoassays had good technical performance and targeted different epitopes of Ng. Absolute Neurogranin ranged from (median+range) 1881 (330-8320) pg/mL for WashU, 372 (71-1191) pg/mL for ADx, and 416 (115-1481) pg/mL for UGot. Spearman correlations between assays were 0.95 (ADx-WashU), 0.87 (UGot-WashU), 0.81 (UGot-ADx). Proportional differences were found between all assays and a systematic difference was found only between WashU and ADx. The assays showed similar Neurogranin distribution patterns for dementia diagnoses – being high in AD compared to the other dementias and controls. Differences in absolute Neurogranin concentrations between the immunoassays were also evaluated by comparisons of the calibrators by SDS-PAGE gels and by Western blot. Conclusions: Results of all three assays are highly correlated. Clinical value of all Neurogranin assays is comparable, while the targeting of different epitopes per assay enables in-depth studies into Neurogranin’s role in AD pathology.
O1-05-05
AMYLOID-PET CONCORDANCE OF ELECSYSÒ CSF BIOMARKER IMMUNOASSAYS FOR ALZHEIMER’S DISEASE
John Seibyl1, Leslie M. Shaw2, Kaj Blennow3, Monika Widmann4, Veronika Corradini5, Simone Wahl6, Katharina Zink6, Katharina Buck6, Udo Eichenlaub6, Oskar Hansson7, 1Molecular Neuroimaging, A Division of inviCRO, New Haven, CT, USA; 2Department of Pathology and Laboratory Medicine, University of Pennsylvania Hospital, Philadelphia, PA, USA; 3Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, M€olndal, Sweden; 4Roche Diagnostics GmbH, Mannheim, Germany; 5Roche Diagnostics GmbH, Rotkreuz, Switzerland; 6Roche Diagnostics GmbH, Penzberg, Germany; 7 Lund University, Malm€o, Sweden. Contact e-mail: jseibyl@mnimaging. com Background: Amyloid-PET imaging with visual analysis is approved by the FDA for Alzheimer’s disease (AD) diagnosis, but is technically complex, costly, and a radiation burden to patients. An alternative is measurement of cerebrospinal fluid (CSF) biomarkers b-Amyloid(1-42) (Ab42), total tau (tTau), and phosphorylated tau (181P) (pTau), for which Roche Diagnostics is developing electrochemiluminescence immunoassays (ElecsysÒ). Using data from the BioFINDER and ADNI cohorts, we assessed whether the ElecsysÒ CSF biomarkers could reliably distinguish amyloid-PET-positive from -negative patients. We also compared visual-read amyloid-PET image analysis vs. the semi-quantitative, standardized uptake value ratios (SUVR) method. Methods: Patients had banked CSF samples and amyloid-PET images, as well as subjective cognitive decline or mild cognitive impairment (BioFINDER, N¼277; 18Fflutemetamol) or mild cognitive impairment or subjective memory complaints, or AD (ADNI, Nz650; 18Fflorbetapir). Three independent readers, blinded to
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Podium Presentations: Sunday, July 16, 2017
clinical data, visually evaluated amyloid-PET scans; amyloid-PET positivity was determined by majority assessment. Intra-reader reliability was determined based on re-ratings of approximately 10% of randomly selected images from available PET scans. Interreader reliability was also assessed. SUVRs were calculated in a standardized cortical region-of-interest using whole cerebellum as the reference region. CSF samples were analyzed using ElecsysÒ immunoassays for Ab42, tTau, and pTau. Results: Data from both ADNI and BioFINDER cohorts will be presented. For BioFINDER, intra-reader reliability based on average positive agreement (APA) and average negative agreement (ANA) was >90%. Inter-reader reliability gave an APA >80% and ANA >90%. Cut-off values for Ab42, pTau/Ab42, and tTau/Ab42 were defined based on visual-read amyloid-PET positivity. The associated positive (PPA) and negative percentage agreements (NPA) at the cut-off value were 91% and 72% for Ab42, and 91% and 89% for both pTau/Ab42 and tTau/Ab42, respectively. Higher concordance could be achieved with reference SUVR. Conclusions: We present a method to determine cut-off values of ElecsysÒ CSF immunoassays based on visual-read amyloid-PET positivity. The ElecsysÒ CSF immunoassays demonstrated excellent ability to predict amyloid-PET positivity, which was further improved by using tTau/ Ab42 and pTau/Ab42 ratios compared to Ab42 alone. O1-05-06
VALIDATION OF CSF TUBES FOR USE ON THE LUMIPULSEÒ G PLATFORM: IMPACT ON Ab1-42
Nathalie Le Bastard, Els Huyck, Jill Vanden Broecke, Fanny Honshoven, Manu Vandijck, Martine Dauwe, Rikkert Maertens, Geert Jannes, Vesna Kostanjevecki, Fujirebio Europe N.V., Gent, Belgium. Contact e-mail: Nathalie.Le. [email protected] Background: The b-amyloid(1-42) (Ab1-42) peptide present in the ce-
rebrospinal fluid (CSF) is known to adsorb to plastics, with Ab1-42 recoveries depending on the type of plastic. The consensus today is that polypropylene tubes should be used for CSF collection and storage. However, it has been shown that even between different polypropylene tubes, Ab1-42 recovery still varies. The new Lumipulse G b-Amyloid 1-42 assay (Fujirebio) was designed for the fully automated analysis of CSF Ab1-42 on the LUMIPULSE G Systems. These instruments allow for the placement of commonly used CSF tubes on the sample carrousel/rack, in addition to the option of using an auto-analyzer cup that is made of polystyrene and commonly used with fully automated instruments. The aim of the current study was to compare the auto-analyzer cup with three different CSF storage tubes in terms of Ab1-42 recovery. Methods: The first experiment compared the Ab1-42 concentration in 17 CSF samples between direct measurement from storage tubes vs. transfer from storage tube to auto-analyzer cup. The second experiment compared the concentrations of the same 17 CSF samples calculated on calibration curves made in the auto-analyzer cups and the three different tubes. In a third experiment, the Ab1-42 recovery in three CSF pools was determined after four consecutive transfers in both the auto-analyzer cup and the storage tubes. Results: The mean Ab1-42 recoveries in the first experiment were 101%, 104% and 104% for transfer to the auto-analyzer cup from tube no. 1, 2 and 3, respectively. There was no impact on Ab1-42 concentration of the tube in which the calibration curve was measured. Consecutive transfers of CSF into the same type of tube gave rise to a maximal drop in Ab1-42 recovery to 89% for the auto-analyzer cup and 59%, 70% and 69% for the respective
CSF storage tubes. Conclusions: The results show that (i) the Lumipulse G b-Amyloid 1-42 concentration is not significantly impacted by a transfer to the auto-analyzer cup, showing that the autoanalyzer cup can be used reliably for the quantitative measurement of CSF Ab1-42, and (ii) confirm the heterogeneity in results obtained in different polypropylene storage tubes. SUNDAY, JULY 16, 2017 ORAL SESSION O1-06 NEUROIMAGING: TAU AND MULTIMODAL BIOMARKER RELATIONSHIPS O1-06-01
REGIONAL AV1451 UPTAKE AND CORTICAL THICKNESS IN RELATION TO MEMORY, LANGUAGE AND EXECUTIVE FUNCTIONING IN AMYLOID-POSITIVE SUBJECTS
Laura E. M. Wisse1, Sandhitsu R. Das1, Long Xie1, Ranjit Ittyerah1, Paul A. Yushkevich1, David A. Wolk2, 1Penn Image Computing and Science Laboratory (PICSL), University of Pennsylvania, Philadelphia, PA, USA; 2 University of Pennsylvania, Philadelphia, PA, USA. Contact e-mail: laura. [email protected] Background: Tau pathology is thought to spread in a characteristic
manner, leading to cell loss and inducing cognitive decline. However, it is unclear to what degree Tau-PET, a marker of neurofibrillary tau pathology (NFT) tracks cognitive symptoms relative to structural MRI, which more directly reflects neuronal injury. In a group of amyloid positive (Ab+) controls, patients with Mild Cognitive Impairment (MCI) and dementia, we investigate the association of memory, language and executive functioning with Tau-PET and MRI-based cortical thickness in brain regions putatively associated with these domains. Methods: We included Ab+ individuals, as determined by Florbetapir PET, (10 controls, 14 MCI and 5 dementia patients) from ADNI who had AV1451 Tau-PET, structural MRI and cognitive data within 6 months of each other. Cortical thickness and normalized SUVR from the Tau-PET scans were measured in regions of interest obtained using multi-atlas segmentation. Composite z-scores of delayed recall, recognition, language and executive functioning were calculated, adjusting for age, gender and education using the linear regression equation from 122 Ab- controls from ADNIGO/2. Results: Significant associations of AV1451 uptake in medial temporal lobe (MTL) structures with memory were found (Table 1), but AV1451 uptake did not correlate significantly with language and executive functioning in regions generally considered to support these functions. Cortical thickness measures were significantly associated with all cognitive domains. Stepwise regression analyses showed that mainly structural measures were significant predictors of memory and executive functioning, but AV1451 uptake was also included in the models for memory (Table 2). None of the predictors significantly predicted language in regression models. Conclusions: These preliminary findings show a stronger association of cognitive functioning with structural brain measures than with AV1451 uptake. Perhaps atrophy provides a tighter link with cognitive decline than tau pathology, possibly because NFTs precede the neurodegeneration which produces cognitive impairment and/or because tau pathology does not capture other contributors to loss of neuronal integrity. The more complementary relationship of AV1451 uptake and structural MRI within the MTL may reflect that in early AD tangle pathology is the primary driver of neuronal integrity in this region, as opposed to language and executive networks.
time-period in which CSF Aß1-42 levels remained stable (20142015). Data-driven cut-points were determined with Gaussian mixture modelling based on raw and corrected CSF data, and diagnostic performance was assessed for each year. Results: Over 15 years time aß1-42 levels showed an upward drift, with a slope depending on diagnosis (pinteraction<.001; figure 1): SCD (beta¼28, SE¼3, p<.001), MCI subjects (beta¼26, SE¼3, p<.001) and dementia other (beta¼26, SE¼4, p<.001 ) showed steeper drifts than AD subjects (beta¼14, SE¼4, p<.001). Mixture-modelling based on drift-corrected and normalised data resulted in a cut-point of 749 pg/ml, providing a stable average sensitivity of 93% (variability over time 4%), which is comparable (p>.05) to a mixture-modelling based cut-point of 680 pg/ml from raw data (92% sensitivity; variability over time 4%) and a more stable and improved specificity (p¼.01) of 86% (variability over time 10%) compared to raw data of 68% specificity, variability over time 24%. Conclusions: Drift effects in Aß1-42 CSF levels over time depend on diagnosis. Adjusting for drift effects in a diagnostic specific way improves and stabilises the specificity performance to distinguish AD from controls. O1-05-04
CLINICAL PERFORMANCE OF NEUROGRANIN AS A CEREBROSPINAL FLUID BIOMARKER FOR ALZHEIMER’S DISEASE: AN ASSAY COMPARISON STUDY
Eline AJ. Willemse1,2,3, Ann De Vos4, Elizabeth M. Herries5, Ulf Andreasson6, Sebastiaan Engelborghs7, Eugeen Vanmechelen8, Wiesje M. van der Flier9,10, Philip Scheltens11, Jack H. Ladenson5, Henrik Zetterberg12,13, Kaj Blennow14, Anne M. Fagan5, Maria Bjerke15, Charlotte E. Teunissen16, 1Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, Antwerp, Belgium; 2Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands; 3Neurochemistry Lab, Clinical Chemistry, VU University Medical Center, Amsterdam, Netherlands; 4ADx NeuroSciences, Ghent, Belgium; 5Washington University School of Medicine, St. Louis, MO, USA; 6Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; 7Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; 8ADx NeuroSciences, Gent, Belgium; 9Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands; 10Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands; 11Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands; 12Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; 13University College London, London, United Kingdom; 14Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, M€ olndal, Sweden; 15Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; 16Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: [email protected] Background: Neurogranin is a postsynaptic protein elevated in cere-
brospinal fluid (CSF) of Alzheimer’s disease (AD) patients. The correlation with cognitive decline evokes promise to use CSF Neurogranin to monitor disease progression. Current assays report divergent ranges of Neurogranin concentrations, and differ in which form of Neurogranin is being measured. This study compares the analytical and clinical performance of three commonly used Neurogranin assays in the same cohort of patients. Methods:
P199
Intra-assay and inter-assay CV, LLOD, calibrators of the other assays, and Neurogranin in brain lysate were measured in: Neurogranin immunoassay performed on an Erenna instrument from WashU (St.Louis, MO), Neurogranin ELISA from ADx NeuroSciences (Ghent, Belgium), and Neurogranin ELISA from UGot (Gothenburg, Sweden). 108 CSF samples from 22 controls with subjective cognitive decline, 22 AD, 22 frontotemporal dementia, 22 dementia with Lewy Bodies, and 20 vascular dementia were selected. Passing-Bablok regression was used to compare the three assays and Kruskal-Wallis was used for Neurogranin group comparisons. Calibrators and antibodies of the three immunoassays were also tested for their reciprocal affinities on Western blot. Results: All immunoassays had good technical performance and targeted different epitopes of Ng. Absolute Neurogranin ranged from (median+range) 1881 (330-8320) pg/mL for WashU, 372 (71-1191) pg/mL for ADx, and 416 (115-1481) pg/mL for UGot. Spearman correlations between assays were 0.95 (ADx-WashU), 0.87 (UGot-WashU), 0.81 (UGot-ADx). Proportional differences were found between all assays and a systematic difference was found only between WashU and ADx. The assays showed similar Neurogranin distribution patterns for dementia diagnoses – being high in AD compared to the other dementias and controls. Differences in absolute Neurogranin concentrations between the immunoassays were also evaluated by comparisons of the calibrators by SDS-PAGE gels and by Western blot. Conclusions: Results of all three assays are highly correlated. Clinical value of all Neurogranin assays is comparable, while the targeting of different epitopes per assay enables in-depth studies into Neurogranin’s role in AD pathology.
O1-05-05
AMYLOID-PET CONCORDANCE OF ELECSYSÒ CSF BIOMARKER IMMUNOASSAYS FOR ALZHEIMER’S DISEASE
John Seibyl1, Leslie M. Shaw2, Kaj Blennow3, Monika Widmann4, Veronika Corradini5, Simone Wahl6, Katharina Zink6, Katharina Buck6, Udo Eichenlaub6, Oskar Hansson7, 1Molecular Neuroimaging, A Division of inviCRO, New Haven, CT, USA; 2Department of Pathology and Laboratory Medicine, University of Pennsylvania Hospital, Philadelphia, PA, USA; 3Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, M€olndal, Sweden; 4Roche Diagnostics GmbH, Mannheim, Germany; 5Roche Diagnostics GmbH, Rotkreuz, Switzerland; 6Roche Diagnostics GmbH, Penzberg, Germany; 7 Lund University, Malm€o, Sweden. Contact e-mail: jseibyl@mnimaging. com Background: Amyloid-PET imaging with visual analysis is approved by the FDA for Alzheimer’s disease (AD) diagnosis, but is technically complex, costly, and a radiation burden to patients. An alternative is measurement of cerebrospinal fluid (CSF) biomarkers b-Amyloid(1-42) (Ab42), total tau (tTau), and phosphorylated tau (181P) (pTau), for which Roche Diagnostics is developing electrochemiluminescence immunoassays (ElecsysÒ). Using data from the BioFINDER and ADNI cohorts, we assessed whether the ElecsysÒ CSF biomarkers could reliably distinguish amyloid-PET-positive from -negative patients. We also compared visual-read amyloid-PET image analysis vs. the semi-quantitative, standardized uptake value ratios (SUVR) method. Methods: Patients had banked CSF samples and amyloid-PET images, as well as subjective cognitive decline or mild cognitive impairment (BioFINDER, N¼277; 18Fflutemetamol) or mild cognitive impairment or subjective memory complaints, or AD (ADNI, Nz650; 18Fflorbetapir). Three independent readers, blinded to
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Podium Presentations: Sunday, July 16, 2017
clinical data, visually evaluated amyloid-PET scans; amyloid-PET positivity was determined by majority assessment. Intra-reader reliability was determined based on re-ratings of approximately 10% of randomly selected images from available PET scans. Interreader reliability was also assessed. SUVRs were calculated in a standardized cortical region-of-interest using whole cerebellum as the reference region. CSF samples were analyzed using ElecsysÒ immunoassays for Ab42, tTau, and pTau. Results: Data from both ADNI and BioFINDER cohorts will be presented. For BioFINDER, intra-reader reliability based on average positive agreement (APA) and average negative agreement (ANA) was >90%. Inter-reader reliability gave an APA >80% and ANA >90%. Cut-off values for Ab42, pTau/Ab42, and tTau/Ab42 were defined based on visual-read amyloid-PET positivity. The associated positive (PPA) and negative percentage agreements (NPA) at the cut-off value were 91% and 72% for Ab42, and 91% and 89% for both pTau/Ab42 and tTau/Ab42, respectively. Higher concordance could be achieved with reference SUVR. Conclusions: We present a method to determine cut-off values of ElecsysÒ CSF immunoassays based on visual-read amyloid-PET positivity. The ElecsysÒ CSF immunoassays demonstrated excellent ability to predict amyloid-PET positivity, which was further improved by using tTau/ Ab42 and pTau/Ab42 ratios compared to Ab42 alone. O1-05-06
VALIDATION OF CSF TUBES FOR USE ON THE LUMIPULSEÒ G PLATFORM: IMPACT ON Ab1-42
Nathalie Le Bastard, Els Huyck, Jill Vanden Broecke, Fanny Honshoven, Manu Vandijck, Martine Dauwe, Rikkert Maertens, Geert Jannes, Vesna Kostanjevecki, Fujirebio Europe N.V., Gent, Belgium. Contact e-mail: Nathalie.Le. [email protected] Background: The b-amyloid(1-42) (Ab1-42) peptide present in the ce-
rebrospinal fluid (CSF) is known to adsorb to plastics, with Ab1-42 recoveries depending on the type of plastic. The consensus today is that polypropylene tubes should be used for CSF collection and storage. However, it has been shown that even between different polypropylene tubes, Ab1-42 recovery still varies. The new Lumipulse G b-Amyloid 1-42 assay (Fujirebio) was designed for the fully automated analysis of CSF Ab1-42 on the LUMIPULSE G Systems. These instruments allow for the placement of commonly used CSF tubes on the sample carrousel/rack, in addition to the option of using an auto-analyzer cup that is made of polystyrene and commonly used with fully automated instruments. The aim of the current study was to compare the auto-analyzer cup with three different CSF storage tubes in terms of Ab1-42 recovery. Methods: The first experiment compared the Ab1-42 concentration in 17 CSF samples between direct measurement from storage tubes vs. transfer from storage tube to auto-analyzer cup. The second experiment compared the concentrations of the same 17 CSF samples calculated on calibration curves made in the auto-analyzer cups and the three different tubes. In a third experiment, the Ab1-42 recovery in three CSF pools was determined after four consecutive transfers in both the auto-analyzer cup and the storage tubes. Results: The mean Ab1-42 recoveries in the first experiment were 101%, 104% and 104% for transfer to the auto-analyzer cup from tube no. 1, 2 and 3, respectively. There was no impact on Ab1-42 concentration of the tube in which the calibration curve was measured. Consecutive transfers of CSF into the same type of tube gave rise to a maximal drop in Ab1-42 recovery to 89% for the auto-analyzer cup and 59%, 70% and 69% for the respective
CSF storage tubes. Conclusions: The results show that (i) the Lumipulse G b-Amyloid 1-42 concentration is not significantly impacted by a transfer to the auto-analyzer cup, showing that the autoanalyzer cup can be used reliably for the quantitative measurement of CSF Ab1-42, and (ii) confirm the heterogeneity in results obtained in different polypropylene storage tubes. SUNDAY, JULY 16, 2017 ORAL SESSION O1-06 NEUROIMAGING: TAU AND MULTIMODAL BIOMARKER RELATIONSHIPS O1-06-01
REGIONAL AV1451 UPTAKE AND CORTICAL THICKNESS IN RELATION TO MEMORY, LANGUAGE AND EXECUTIVE FUNCTIONING IN AMYLOID-POSITIVE SUBJECTS
Laura E. M. Wisse1, Sandhitsu R. Das1, Long Xie1, Ranjit Ittyerah1, Paul A. Yushkevich1, David A. Wolk2, 1Penn Image Computing and Science Laboratory (PICSL), University of Pennsylvania, Philadelphia, PA, USA; 2 University of Pennsylvania, Philadelphia, PA, USA. Contact e-mail: laura. [email protected] Background: Tau pathology is thought to spread in a characteristic
manner, leading to cell loss and inducing cognitive decline. However, it is unclear to what degree Tau-PET, a marker of neurofibrillary tau pathology (NFT) tracks cognitive symptoms relative to structural MRI, which more directly reflects neuronal injury. In a group of amyloid positive (Ab+) controls, patients with Mild Cognitive Impairment (MCI) and dementia, we investigate the association of memory, language and executive functioning with Tau-PET and MRI-based cortical thickness in brain regions putatively associated with these domains. Methods: We included Ab+ individuals, as determined by Florbetapir PET, (10 controls, 14 MCI and 5 dementia patients) from ADNI who had AV1451 Tau-PET, structural MRI and cognitive data within 6 months of each other. Cortical thickness and normalized SUVR from the Tau-PET scans were measured in regions of interest obtained using multi-atlas segmentation. Composite z-scores of delayed recall, recognition, language and executive functioning were calculated, adjusting for age, gender and education using the linear regression equation from 122 Ab- controls from ADNIGO/2. Results: Significant associations of AV1451 uptake in medial temporal lobe (MTL) structures with memory were found (Table 1), but AV1451 uptake did not correlate significantly with language and executive functioning in regions generally considered to support these functions. Cortical thickness measures were significantly associated with all cognitive domains. Stepwise regression analyses showed that mainly structural measures were significant predictors of memory and executive functioning, but AV1451 uptake was also included in the models for memory (Table 2). None of the predictors significantly predicted language in regression models. Conclusions: These preliminary findings show a stronger association of cognitive functioning with structural brain measures than with AV1451 uptake. Perhaps atrophy provides a tighter link with cognitive decline than tau pathology, possibly because NFTs precede the neurodegeneration which produces cognitive impairment and/or because tau pathology does not capture other contributors to loss of neuronal integrity. The more complementary relationship of AV1451 uptake and structural MRI within the MTL may reflect that in early AD tangle pathology is the primary driver of neuronal integrity in this region, as opposed to language and executive networks.