%0 Journal Article
%A Biechele, Gloria
%A Sebastian Monasor, Laura
%A Wind, Karin
%A Blume, Tanja
%A Parhizkar, Samira
%A Arzberger, Thomas
%A Sacher, Christian
%A Beyer, Leonie
%A Eckenweber, Florian
%A Gildehaus, Franz-Josef
%A von Ungern-Sternberg, Barbara
%A Willem, Michael
%A Bartenstein, Peter
%A Cumming, Paul
%A Rominger, Axel
%A Herms, Jochen
%A Lichtenthaler, Stefan F
%A Haass, Christian
%A Tahirovic, Sabina
%A Brendel, Matthias
%T Glitter in the Darkness? Nonfibrillar β-Amyloid Plaque Components Significantly Impact the β-Amyloid PET Signal in Mouse Models of Alzheimer Disease.
%J Journal of nuclear medicine
%V 63
%N 1
%@ 0022-3123
%C New York, NY
%I Soc.
%M DZNE-2022-00669
%P 117 - 124
%D 2022
%X β-amyloid (Aβ) PET is an important tool for quantification of amyloidosis in the brain of suspected Alzheimer disease (AD) patients and transgenic AD mouse models. Despite the excellent correlation of Aβ PET with gold standard immunohistochemical assessments, the relative contributions of fibrillar and nonfibrillar Aβ components to the in vivo Aβ PET signal remain unclear. Thus, we obtained 2 murine cerebral amyloidosis models that present with distinct Aβ plaque compositions and performed regression analysis between immunohistochemistry and Aβ PET to determine the biochemical contributions to Aβ PET signal in vivo. Methods: We investigated groups of AppNL-G-F and APPPS1 mice at 3, 6, and 12 mo of age by longitudinal 18F-florbetaben Aβ PET and with immunohistochemical analysis of the fibrillar and total Aβ burdens. We then applied group-level intermodality regression models using age- and genotype-matched sets of fibrillar and nonfibrillar Aβ data (predictors) and Aβ PET results (outcome) for both Aβ mouse models. An independent group of double-hit APPPS1 mice with dysfunctional microglia due to knockout of triggering receptor expression on myeloid cells 2 (Trem2-/-) served for validation and evaluation of translational impact. Results: Neither fibrillar nor nonfibrillar Aβ content alone sufficed to explain the Aβ PET findings in either AD model. However, a regression model compiling fibrillar and nonfibrillar Aβ together with the estimate of individual heterogeneity and age at scanning could explain a 93
%K Plaque, Amyloid
%K PET signal (Other)
%K amyloid (Other)
%K fibrillar (Other)
%K mouse (Other)
%K nonfibrillar (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34016733
%2 pmc:PMC8717179
%R 10.2967/jnumed.120.261858
%U https://pub.dzne.de/record/164000