Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β‐amyloid
Open accessAbstract
Objective: We examined agreement and disagreement between 2 biomarkers of β‐amyloid (Aβ) deposition (amyloid positron emission tomography [PET] and cerebrospinal fluid [CSF] Aβ 1–42 ) 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. Ann Neurol 2013;74:826–836
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The continuous relationship between CSF Aβ42 and amyloid PET is "L-shaped" rather than linear.
“The continuous relationship between CSF Aβ42 and amyloid PET, however, is “L-shaped” rather than linear [116,117,120].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [116]
The Discussion (page not available in our copy) says that CSF Aβ and florbetapir PET have a nonlinear inverse relationship when plotted against each other. The Results describe the relationship between their continuous measurements. Neither passage establishes the more specific “L-shaped” description. (LLM, conf=0.82)
Experimental — accuracy not yet measuredDiscordances between imaging and CSF biomarkers may occur.
“Discordances between imaging and CSF biomarkers may occur [36,41,116–119].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [116]
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References 36 · Cited by 401
Research works printed but not linked: 30
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- Authors
- Landau, S. M., Lu, M., Joshi, A. D., Pontecorvo, M., Mintun, M. A., Trojanowski, J. Q., Shaw, L. M., Jagust, W. J., & Initiative, F. T. A. D. N.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Avid Radiopharmaceuticals (United States) (US)
- University of Pennsylvania (US)
- Corresponding author
- Landau, Susan M.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2013-12
- Volume
- 74
- Issue
- 6
- Pages
- 826-836
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC3748164
- OpenAlex
- W2133649359
- Cited by
- 401
- References
- 36
- Citations by year
- 2026: 14 · 2025: 32 · 2024: 38 · 2023: 24 · 2022: 33 · 2021: 40 · 2020: 32 · 2019: 33 · 2018: 32 · 2017: 29 · 2016: 32 · 2015: 32 · 2014: 26 · 2013: 4
- FWCI
- 22.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (U01 AG024904, P30 AG010129, K01 AG030514)
- National Institute on Aging and National Institute of Biomedical Imaging and Bioengineering
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- amyloid-beta, amyloid PET, cerebrospinal fluid biomarkers, florbetapir, amyloid-beta 42, Alzheimer's disease, mild cognitive impairment, CSF tau, APOE ε4, normal aging, early disease detection
- MeSH terms
- Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Cross-Sectional Studies, Ethylene Glycols, Female, Humans, Longitudinal Studies, Male, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, Positron-Emission Tomography, Cognitive Dysfunction
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