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Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β-amyloid.
Ann Neurol. 2013 Dec; 74(6):826-36.AN

Abstract

OBJECTIVE

We examined agreement and disagreement between 2 biomarkers of β-amyloid (Aβ) deposition (amyloid positron emission tomography [PET] and cerebrospinal fluid [CSF] Aβ1-42) in normal aging and dementia in a large multicenter study.

METHODS

Concurrently acquired florbetapir PET and CSF Aβ were measured in cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease participants (n = 374) from the Alzheimer's Disease Neuroimaging Initiative. We also compared Aβ measurements in a separate group with serial CSF measurements over 3.1 ± 0.8 years that preceded a single florbetapir session. Additional biomarker and cognitive data allowed us to further examine profiles of discordant cases.

RESULTS

Florbetapir and CSF Aβ were inversely correlated across all diagnostic groups, and dichotomous measurements were in agreement in 86% of subjects. Among subjects showing the most disagreement, the 2 discordant groups had different profiles: the florbetapir(+) /CSF Aβ(-) group was larger (n = 13) and was made up of only normal and early MCI subjects, whereas the florbetapir(-) /CSF Aβ(+) group was smaller (n = 7) and had poorer cognitive function and higher CSF tau, but no ApoE4 carriers. In the longitudinal sample, we observed both stable longitudinal CSF Aβ trajectories and those actively transitioning from normal to abnormal, but the final CSF Aβ measurements were in good agreement with florbetapir cortical retention.

INTERPRETATION

CSF and amyloid PET measurements of Aβ were consistent in the majority of subjects in the cross-sectional and longitudinal populations. Based on our analysis of discordant subjects, the available evidence did not show that CSF Aβ regularly becomes abnormal prior to fibrillar Aβ accumulation early in the course of disease.

Authors+Show Affiliations

Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23536396

Citation

Landau, Susan M., et al. "Comparing Positron Emission Tomography Imaging and Cerebrospinal Fluid Measurements of Β-amyloid." Annals of Neurology, vol. 74, no. 6, 2013, pp. 826-36.
Landau SM, Lu M, Joshi AD, et al. Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β-amyloid. Ann Neurol. 2013;74(6):826-36.
Landau, S. M., Lu, M., Joshi, A. D., Pontecorvo, M., Mintun, M. A., Trojanowski, J. Q., Shaw, L. M., & Jagust, W. J. (2013). Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β-amyloid. Annals of Neurology, 74(6), 826-36. https://doi.org/10.1002/ana.23908
Landau SM, et al. Comparing Positron Emission Tomography Imaging and Cerebrospinal Fluid Measurements of Β-amyloid. Ann Neurol. 2013;74(6):826-36. PubMed PMID: 23536396.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β-amyloid. AU - Landau,Susan M, AU - Lu,Ming, AU - Joshi,Abhinay D, AU - Pontecorvo,Michael, AU - Mintun,Mark A, AU - Trojanowski,John Q, AU - Shaw,Leslie M, AU - Jagust,William J, AU - ,, PY - 2012/12/21/received PY - 2013/02/08/revised PY - 2013/03/18/accepted PY - 2013/3/29/entrez PY - 2013/3/29/pubmed PY - 2014/3/19/medline SP - 826 EP - 36 JF - Annals of neurology JO - Ann. Neurol. VL - 74 IS - 6 N2 - OBJECTIVE: We examined agreement and disagreement between 2 biomarkers of β-amyloid (Aβ) deposition (amyloid positron emission tomography [PET] and cerebrospinal fluid [CSF] Aβ1-42) in normal aging and dementia in a large multicenter study. METHODS: Concurrently acquired florbetapir PET and CSF Aβ were measured in cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease participants (n = 374) from the Alzheimer's Disease Neuroimaging Initiative. We also compared Aβ measurements in a separate group with serial CSF measurements over 3.1 ± 0.8 years that preceded a single florbetapir session. Additional biomarker and cognitive data allowed us to further examine profiles of discordant cases. RESULTS: Florbetapir and CSF Aβ were inversely correlated across all diagnostic groups, and dichotomous measurements were in agreement in 86% of subjects. Among subjects showing the most disagreement, the 2 discordant groups had different profiles: the florbetapir(+) /CSF Aβ(-) group was larger (n = 13) and was made up of only normal and early MCI subjects, whereas the florbetapir(-) /CSF Aβ(+) group was smaller (n = 7) and had poorer cognitive function and higher CSF tau, but no ApoE4 carriers. In the longitudinal sample, we observed both stable longitudinal CSF Aβ trajectories and those actively transitioning from normal to abnormal, but the final CSF Aβ measurements were in good agreement with florbetapir cortical retention. INTERPRETATION: CSF and amyloid PET measurements of Aβ were consistent in the majority of subjects in the cross-sectional and longitudinal populations. Based on our analysis of discordant subjects, the available evidence did not show that CSF Aβ regularly becomes abnormal prior to fibrillar Aβ accumulation early in the course of disease. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/23536396/Comparing_positron_emission_tomography_imaging_and_cerebrospinal_fluid_measurements_of_β_amyloid_ L2 - https://doi.org/10.1002/ana.23908 DB - PRIME DP - Unbound Medicine ER -