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61/100

✓ Peer-reviewed alzhub usefulness score 61 out of 100. Genetics

Topic: Amyloid, tau and blood-test diagnosis

Importance Cerebrospinal fluid (CSF) and positron emission tomographic (PET) amyloid biomarkers have been proposed for the detection of Alzheimer disease (AD) pathology in living patients and for the tracking of longitudinal changes, but the relation between biomarkers needs further study. Objective To determine the association between CSF and PET amyloid biomarkers (cross-sectional and longitudinal measures) and compare the cutoffs for these measures. Design, setting, and participants Longitudinal clinical cohort study from 2005 to 2014 including 820 participants with at least 1 florbetapir F-18 (hereafter referred to as simply florbetapir)-PET scan and at least 1 CSF β-amyloid 1-42 (Aβ1-42) sample obtained within 30 days of each other (501 participants had a second PET scan after 2 years, including 150 participants with CSF Aβ1-42 measurements). Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Main outcomes and measures Four different PET scans processing pipelines from 2 different laboratories were compared. The PET cutoff values were established using a mixture-modeling approach, and different mathematical models were applied to define the association between CSF and PET amyloid measures. Results The values of the CSF Aβ1-42 samples and florbetapir-PET scans showed a nonlinear association (R2 = 0.48-0.66), with the strongest association for values in the middle range. The presence of a larger dynamic range of florbetapir-PET scan values in the higher range compared with the CSF Aβ1-42 plateau explained the differences in correlation with cognition (R2 = 0.36 and R2 = 0.25, respectively). The APOE genotype significantly modified the association between both biomarkers. The PET cutoff values derived from an unsupervised classifier converged with previous PET cutoff values and the established CSF Aβ1-42 cutoff levels. There was no association between longitudinal Aβ1-42 levels and standardized uptake value ratios during follow-up. Conclusions and relevance The association between both biomarkers is limited to a middle range of values, is modified by the APOE genotype, and is absent for longitudinal changes; 4 different approaches in 2 different platforms converge on similar pathological Aβ cutoff levels; and different pipelines to process PET scans showed correlated but not identical results. Our findings suggest that both biomarkers measure different aspects of AD Aβ pathology.

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APA 7th

Toledo, J. B., Bjerke, M., Da, X., Landau, S. M., Foster, N. L., Jagust, W., et al. (2015). Nonlinear Association Between Cerebrospinal Fluid and Florbetapir F-18 β-Amyloid Measures Across the Spectrum of Alzheimer Disease. JAMA neurology. https://doi.org/10.1001/jamaneurol.2014.4829

Vancouver

Toledo JB, Bjerke M, Da X, Landau SM, Foster NL, Jagust W, et al. Nonlinear Association Between Cerebrospinal Fluid and Florbetapir F-18 β-Amyloid Measures Across the Spectrum of Alzheimer Disease. JAMA neurology. 2015. doi:10.1001/jamaneurol.2014.4829. PMID: 25822737.

BibTeX

@article{toledo2015-25822737,
  author  = {Toledo, J. B. and Bjerke, M. and Da, X. and Landau, S. M. and Foster, N. L. and Jagust, W. and Jack, C. and Weiner, M. and others},
  title   = {{Nonlinear Association Between Cerebrospinal Fluid and Florbetapir F-18 β-Amyloid Measures Across the Spectrum of Alzheimer Disease}},
  journal = {JAMA neurology},
  year    = {2015},
  doi     = {10.1001/jamaneurol.2014.4829},
  pmid    = {25822737},
  url     = {https://doi.org/10.1001/jamaneurol.2014.4829}
}

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Key findings

Results The values of the CSF Aβ1-42 samples and florbetapir-PET scans showed a nonlinear association (R2 = 0.48-0.66), with the strongest association for values in the middle range.
The presence of a larger dynamic range of florbetapir-PET scan values in the higher range compared with the CSF Aβ1-42 plateau explained the differences in correlation with cognition (R2 = 0.36 and R2 = 0.25, respectively).
The APOE genotype significantly modified the association between both biomarkers.
Conclusions and relevance The association between both biomarkers is limited to a middle range of values, is modified by the APOE genotype, and is absent for longitudinal changes; 4 different approaches in 2 different platforms converge on similar pathological Aβ cutoff levels; and different pipelines to process PET scans showed correlated but not identical results.
Our findings suggest that both biomarkers measure different aspects of AD Aβ pathology.

Why it matters

Spinal fluid and PET amyloid measures were related in a nonlinear way across 820 participants, and APOE genotype modified that relationship. This compares two ways of measuring amyloid and does not test any treatment.

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Study details

Study designcohort study
Participants820
Evidence strengthModerate

How this study scored 61/100

Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (JAMA neurology)
Journal's citation record	2 / 4	JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29)
Study design	7 / 12	A cohort study following people over time
Strength of evidence	3 / 5	Rated “moderate” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	1 / 5	2015 — within 20 year(s) of the newest study here
Sample size	2 / 4	820 participants
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	4 / 7	Cited 88 times (OpenAlex, 2026-10-10)
Citations per year	2 / 5	6.8 citations a year over 13 year(s) since 2015
Impact for its field and year	4 / 6	Cited 10.6× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	3 / 6	Cited by 12 other studies in this library
Still being cited	1 / 4	Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author John Q. Trojanowski: h-index 255 (OpenAlex, whole career)
Institution's track record	2 / 3	University of California, Berkeley: institution h-index 2,012 (OpenAlex)
Multi-centre collaboration	2 / 3	OpenAlex lists 6 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 25822737)
Free to read	0 / 2	Behind a paywall — scores zero
Total	61 / 100	—

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