Marissa Zwan1, Argonde van Harten2, Rik Ossenkoppele1, Femke Bouwman2, Charlotte Teunissen3, Sofie Adriaanse1, Adriaan Lammertsma4, Philip Scheltens2, Bart van Berckel4, Wiesje van der Flier5. 1. Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands Department of Radiology & Nuclear Medicine, VU University Medical Center, MB Amsterdam, The Netherlands. 2. Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands. 3. Department of Epidemiology and Biostatistics, VU University Medical Center, MB Amsterdam, The Netherlands. 4. Department of Radiology & Nuclear Medicine, VU University Medical Center, MB Amsterdam, The Netherlands. 5. Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands Department of Epidemiology and Biostatistics, VU University Medical Center, MB Amsterdam, The Netherlands.
Abstract
BACKGROUND: Two approaches are available for measuring Alzheimer's disease (AD) pathology in vivo. Biomarkers in cerebrospinal fluid (CSF) include amyloid-β1-42 (Aβ42) and tau. Furthermore, amyloid deposition can be visualized using positron emission tomography (PET) and [11C]Pittsburgh compound-B ([11C]PIB). OBJECTIVE: We investigated concordance between CSF biomarkers and [11C]PIB PET as markers for AD pathology in a memory clinic cohort. METHODS: We included 64 AD patients, 34 non-AD dementia patients, 22 patients with mild cognitive impairment (MCI), and 16 controls. [11C]PIB scans were visually rated as positive or negative. CSF biomarkers were considered abnormal based on Aβ42 alone (<550 ng/L), a more lenient Aβ42 cut-off (<640 ng/L) or a combination of both Aβ42 and tau ((373 + 0.82 tau)/Aβ42 > 1). Concordance between CSF biomarkers and [11C]PIB PET was determined. RESULTS: Overall, concordance between [11C]PIB PET and CSF Aβ42 (<550 ng/L) was 84%. In discordant cases, [11C]PIB PET was more often AD-positive than Aβ42. When a more lenient Aβ42 cut-point (<640 ng/L) or a combination of Aβ42 and tau was used, concordance with [11C]PIB PET appeared to be even higher (90% and 89%). This difference is explained by a subgroup of mostly MCI and AD patients with Aβ42 levels just above cut-off. Now, in discordant cases, CSF was more often AD-positive than [11C]PIB PET. CONCLUSION: Concordance between CSF Aβ42 and [11C]PIB PET was good in all diagnostic groups. Discordance was mostly seen in MCI and AD patients close to the cut-point. These results provide convergent validity for the use of both types of biomarkers as measures of AD pathology.
BACKGROUND: Two approaches are available for measuring Alzheimer's disease (AD) pathology in vivo. Biomarkers in cerebrospinal fluid (CSF) include amyloid-β1-42 (Aβ42) and tau. Furthermore, amyloid deposition can be visualized using positron emission tomography (PET) and [11C]Pittsburgh compound-B ([11C]PIB). OBJECTIVE: We investigated concordance between CSF biomarkers and [11C]PIB PET as markers for AD pathology in a memory clinic cohort. METHODS: We included 64 ADpatients, 34 non-AD dementiapatients, 22 patients with mild cognitive impairment (MCI), and 16 controls. [11C]PIB scans were visually rated as positive or negative. CSF biomarkers were considered abnormal based on Aβ42 alone (<550 ng/L), a more lenient Aβ42 cut-off (<640 ng/L) or a combination of both Aβ42 and tau ((373 + 0.82 tau)/Aβ42 > 1). Concordance between CSF biomarkers and [11C]PIB PET was determined. RESULTS: Overall, concordance between [11C]PIB PET and CSF Aβ42 (<550 ng/L) was 84%. In discordant cases, [11C]PIB PET was more often AD-positive than Aβ42. When a more lenient Aβ42 cut-point (<640 ng/L) or a combination of Aβ42 and tau was used, concordance with [11C]PIB PET appeared to be even higher (90% and 89%). This difference is explained by a subgroup of mostly MCI and ADpatients with Aβ42 levels just above cut-off. Now, in discordant cases, CSF was more often AD-positive than [11C]PIB PET. CONCLUSION: Concordance between CSF Aβ42 and [11C]PIB PET was good in all diagnostic groups. Discordance was mostly seen in MCI and ADpatients close to the cut-point. These results provide convergent validity for the use of both types of biomarkers as measures of AD pathology.
Entities:
Keywords:
Alzheimer's disease; amyloid; cerebrospinal fluid; positron-emission tomography; tau
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