Not quite PIB-positive, not quite PIB-negative: Slight PIB elevations in elderly normal control subjects are biologically relevant
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Researchers employing Pittsburgh Compound B positron emission tomography (PIB-PET) imaging have consistently indentified old normal control (oNC) subjects with elevated tracer uptake, suggesting the presence of beta-amyloid deposition in these individuals. However, a consensus regarding the level at which PIB reveals a biologically meaningful signal does not exist (ie. an appropriate cutoff value for PIB positivity remains unclear). In this exploratory study, we sought to investigate the range of PIB distribution volume ratio (DVR) values present in our oNC cohort (N=75, age range=58-97). oNC subjects were classified based on global PIB index values (average DVR across prefrontal, parietal, lateral temporal and cingulate cortices) by employing two approaches: (1) an iterative outlier approach that revealed a cutoff value of 1.16 (IO-cutoff) and (2) an approach using data from a sample of young normal control subjects (N=11, age range=20-30) that yielded a cutoff value of 1.08 (yNC-cutoff). oNC subjects falling above the IO-cutoff had values similar to AD subjects ("PIB+", 15%). Subjects falling between the 2 cutoffs were considered to have ambiguous PIB status ("Ambig", 20%) and the remaining oNC were considered "PIB-" (65%). Additional measures capturing focal DVR magnitude and extent of elevated DVR values were consistent with the classification scheme using PIB index values, and revealed evidence for elevated DVR values in a subset of PIB- oNC subjects. Furthermore, there were a greater proportion of ambiguously elevated values compared to low values, and these elevated values were present in regions known to show amyloid deposition. The analyses presented in this study, in conjunction with recently published pathological data, suggest a biological relevance of slight PIB elevations in aging.
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Universal standards for imaging and CSF biomarker measures have not yet been established.
“These efforts are the subject of ongoing research, but universal standards have not yet been established [201].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [201]
Section 4.7 of the Discussion (page not provided) says the PIB-PET cutoff is arbitrary, may differ across cohorts, and may not apply to other laboratories. This supports the lack of a universal standard for that imaging measure, but the paper does not establish the same point for CSF biomarker measures or imaging measures generally. (LLM, conf=0.85)
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- Mintun MA Larossa GN Sheline YI Dence CS Lee SY Mach RH Klunk WE Mathis CA DeKosky ST Morris JC [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 2006 67 446 452 16894106
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Self-citation
- Authors
- Mormino, E. C., Brandel, M. G., Madison, C. M., Rabinovici, G. D., Marks, S., Baker, S. L., & Jagust, W. J.
- Affiliations
- University of California, Berkeley (US)
- University of California, San Francisco (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Mormino, Elizabeth C.
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 59
- Issue
- 2
- Pages
- 1152-1160
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3230690
- OpenAlex
- W2010021812
- Cited by
- 158
- References
- 43
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 11 · 2023: 7 · 2022: 7 · 2021: 15 · 2020: 13 · 2019: 12 · 2018: 7 · 2017: 12 · 2016: 9 · 2015: 8 · 2014: 18 · 2013: 19 · 2012: 7
- FWCI
- 10.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (AG034570, AG032814)
- Alzheimer's Association (ZEN-08-87090)
- 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
- Pittsburgh compound B, PiB PET, amyloid-beta deposition, distribution volume ratio, Alzheimer's disease, aging, amyloid imaging
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Aniline Compounds, Brain, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, Thiazoles, Tissue Distribution, Reproducibility of Results, Radiopharmaceuticals, Positron-Emission Tomography, Benzothiazoles, Young Adult
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