Affiliations: [a] Department of Neurology and Alzheimer Center, VU University Medical Center, MB Amsterdam, The Netherlands | [b] Department of Radiology & Nuclear Medicine, VU University Medical Center, MB Amsterdam, The Netherlands | [c] Department of Epidemiology and Biostatistics, VU University Medical Center, MB Amsterdam, The Netherlands
Correspondence:
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Correspondence to: Marissa D. Zwan, Alzheimer Center & Department of Neurology and Department of Radiology & Nuclear Medicine, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. Tel.: +31 20 444 0685; Fax: +31 20 444 0715; E-mail: m.zwan@vumc.nl.
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 + 0.82tau)/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.
Keywords: Alzheimer's disease, amyloid, cerebrospinal fluid, positron-emission tomography, tau
