Comparing amyloid-β plaque burden with antemortem PiB PET in autosomal dominant and late-onset Alzheimer disease

Charles D. Chen, Nelly Joseph-Mathurin, Namita Sinha, Aihong Zhou, Yan Li, Karl Friedrichsen, Austin McCullough, Erin E. Franklin, Russ Hornbeck, Brian Gordon, Vijay Sharma, Carlos Cruchaga, Alison Goate, Celeste Karch, Eric McDade, Chengjie Xiong, Randall J. Bateman, Bernardino Ghetti, John M. Ringman, Jasmeer ChhatwalColin L. Masters, Catriona McLean, Tammaryn Lashley, Yi Su, Robert Koeppe, Clifford Jack, William E. Klunk, John C. Morris, Richard J. Perrin, Nigel J. Cairns, Tammie L.S. Benzinger

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Pittsburgh compound B (PiB) radiotracer for positron emission tomography (PET) imaging can bind to different types of amyloid-β plaques and blood vessels (cerebral amyloid angiopathy). However, the relative contributions of different plaque subtypes (diffuse versus cored/compact) to in vivo PiB PET signal on a region-by-region basis are incompletely understood. Of particular interest is whether the same staging schemes for summarizing amyloid-β burden are appropriate for both late-onset and autosomal dominant forms of Alzheimer disease (LOAD and ADAD). Here, we compared antemortem PiB PET with follow-up postmortem estimation of amyloid-β burden using stereologic methods to estimate the relative area fraction of diffuse and cored/compact amyloid-β plaques across 16 brain regions in 15 individuals with ADAD and 14 individuals with LOAD. In ADAD, we found that PiB PET correlated with diffuse plaques in the frontal, parietal, temporal, and striatal regions commonly used to summarize amyloid-β burden in PiB PET, and correlated with both diffuse and cored/compact plaques in the occipital lobe and parahippocampal gyrus. In LOAD, we found that PiB PET correlated with both diffuse and cored/compact plaques in the anterior cingulate, frontal lobe (middle frontal gyrus), and parietal lobe, and showed additional correlations with diffuse plaque in the amygdala and occipital lobe, and with cored/compact plaque in the temporal lobe. Thus, commonly used PiB PET summary regions predominantly reflect diffuse plaque burden in ADAD and a mixture of diffuse and cored/compact plaque burden in LOAD. In direct comparisons of ADAD and LOAD, postmortem stereology identified much greater mean amyloid-β plaque burdens in ADAD versus LOAD across almost all brain regions studied. However, standard PiB PET did not recapitulate these stereologic findings, likely due to non-trivial amyloid-β plaque burdens in ADAD within the cerebellum and brainstem—commonly used reference regions in PiB PET. Our findings suggest that PiB PET summary regions correlate with amyloid-β plaque burden in both ADAD and LOAD; however, they might not be reliable in direct comparisons of regional amyloid-β plaque burden between the two forms of AD.

Original languageEnglish
Pages (from-to)689-706
Number of pages18
JournalActa Neuropathologica
Volume142
Issue number4
DOIs
StatePublished - Oct 2021

Keywords

  • Alzheimer disease
  • Amyloid-β plaques
  • PiB PET
  • Stereology

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