11C-PiB PET can underestimate brain amyloid-β burden when cotton wool plaques are numerous.

Autor:	Abrahamson EE; Department of Neurology, University of Pittsburgh School of Medicine. Pittsburgh, PA, USA.; Geriatric Research Education and Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh, PA, USA., Kofler JK; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Becker CR; Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Price JC; Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Massachusetts General Hospital, A. A. Martinos Center for Biomedical Imaging, Cambridge, MA, USA., Newell KL; Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA., Ghetti B; Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA., Murrell JR; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., McLean CA; Victorian Brain Bank, The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia., Lopez OL; Department of Neurology, University of Pittsburgh School of Medicine. Pittsburgh, PA, USA., Mathis CA; Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Klunk WE; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Villemagne VL; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.; School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia., Ikonomovic MD; Department of Neurology, University of Pittsburgh School of Medicine. Pittsburgh, PA, USA.; Geriatric Research Education and Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh, PA, USA.; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2022 Jun 30; Vol. 145 (6), pp. 2161-2176.
DOI:	10.1093/brain/awab434
Abstrakt:	Individuals with familial Alzheimer's disease due to PSEN1 mutations develop high cortical fibrillar amyloid-β load but often have lower cortical 11C-Pittsburgh compound B (PiB) retention than Individuals with sporadic Alzheimer's disease. We hypothesized this is influenced by limited interactions of Pittsburgh compound B with cotton wool plaques, an amyloid-β plaque type common in familial Alzheimer's disease but rare in sporadic Alzheimer's disease. Histological sections of frontal and temporal cortex, caudate nucleus and cerebellum were obtained from 14 cases with sporadic Alzheimer's disease, 12 cases with familial Alzheimer's disease due to PSEN1 mutations, two relatives of a PSEN1 mutation carrier but without genotype information and three non-Alzheimer's disease cases. Sections were processed immunohistochemically using amyloid-β-targeting antibodies and the fluorescent amyloid stains cyano-PiB and X-34. Plaque load was quantified by percentage area analysis. Frozen homogenates from the same brain regions from five sporadic Alzheimer's disease and three familial Alzheimer's disease cases were analysed for 3H-PiB in vitro binding and concentrations of amyloid-β1-40 and amyloid-β1-42. Nine sporadic Alzheimer's disease, three familial Alzheimer's disease and three non-Alzheimer's disease participants had 11C-PiB PET with standardized uptake value ratios calculated using the cerebellum as the reference region. Cotton wool plaques were present in the neocortex of all familial Alzheimer's disease cases and one sporadic Alzheimer's disease case, in the caudate nucleus from four familial Alzheimer's disease cases, but not in the cerebellum. Cotton wool plaques immunolabelled robustly with 4G8 and amyloid-β42 antibodies but weakly with amyloid-β40 and amyloid-βN3pE antibodies and had only background cyano-PiB fluorescence despite labelling with X-34. Relative to amyloid-β plaque load, cyano-Pittsburgh compound B plaque load was similar in sporadic Alzheimer's disease while in familial Alzheimer's disease it was lower in the neocortex and the caudate nucleus. In both regions, insoluble amyloid-β1-42 and amyloid-β1-40 concentrations were similar in familial Alzheimer's disease and sporadic Alzheimer's disease groups, while 3H-PiB binding was lower in the familial Alzheimer's disease than the sporadic Alzheimer's disease group. Higher amyloid-β1-42 concentration associated with higher 3H-PiB binding in sporadic Alzheimer's disease but not familial Alzheimer's disease. 11C-PiB retention correlated with region-matched post-mortem amyloid-β plaque load; however, familial Alzheimer's disease cases with abundant cotton wool plaques had lower 11C-PiB retention than sporadic Alzheimer's disease cases with similar amyloid-β plaque loads. PiB has limited ability to detect amyloid-β aggregates in cotton wool plaques and may underestimate total amyloid-β plaque burden in brain regions with abundant cotton wool plaques. (Published by Oxford University Press on behalf of the Guarantors of Brain 2021.)
Databáze:	MEDLINE
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