| Title: |
11C-PiB PET can underestimate brain amyloid-β burden when cotton wool plaques are numerous |
| Authors: |
Abrahamson, EE; Kofler, JK; Becker, CR; Price, JC; Newell, KL; Ghetti, B; Murrell, JR; Mclean, CA; Lopez, OL; Mathis, CA; Klunk, WE; Villemagne, VL; Ikonomovic, MD |
| Publisher Information: |
OXFORD UNIV PRESS |
| Publication Year: |
2022 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0006-8950 |
| Relation: |
NHMRC/1046471; pii: 6464340; https://hdl.handle.net/11343/333176 |
| Availability: |
https://hdl.handle.net/11343/333176 |
| Accession Number: |
edsbas.57C95817 |
| Database: |
BASE |