Glitter in the Darkness? Nonfibrillar β-Amyloid Plaque Components Significantly Impact the β-Amyloid PET Signal in Mouse Models of Alzheimer Disease
| Autor: | Franz-Josef Gildehaus, Samira Parhizkar, Florian Eckenweber, Matthias Brendel, Axel Rominger, Sabina Tahirovic, Leonie Beyer, Laura Sebastian Monasor, Tanja Blume, Peter Bartenstein, Christian Haass, Christian Sacher, Thomas Arzberger, Gloria Biechele, Jochen Herms, Karin Wind, Stefan F. Lichtenthaler, Barbara von Ungern-Sternberg, Paul Cumming, Michael Willem |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Pathology
medicine.medical_specialty Amyloid Microglia TREM2 Chemistry Amyloidosis Transgene Receptor expression fibrillar nonfibrillar amyloid 610 Medicine & health Plaque Amyloid medicine.disease medicine.anatomical_structure PET signal In vivo medicine Immunohistochemistry Radiology Nuclear Medicine and imaging ddc:610 mouse |
| Zdroj: | Journal of nuclear medicine 63(1), 117-124 (2022). doi:10.2967/jnumed.120.261858 Biechele, Gloria; Sebastian Monasor, Laura; Wind, Karin; Blume, Tanja; Parhizkar, Samira; Arzberger, Thomas; Sacher, Christian; Beyer, Leonie; Eckenweber, Florian; Gildehaus, Franz-Josef; von Ungern-Sternberg, Barbara; Willem, Michael; Bartenstein, Peter; Cumming, Paul; Rominger, Axel; Herms, Jochen; Lichtenthaler, Stefan; Haass, Christian; Tahirovic, Sabina and Brendel, Matthias (2022). Glitter in the Darkness? Non-fibrillar β-amyloid Plaque Components Significantly Impact the β-amyloid PET Signal in Mouse Models of Alzheimer's Disease. Journal of nuclear medicine, 63(1), pp. 117-124. Society of Nuclear Medicine 10.2967/jnumed.120.261858 |
| DOI: | 10.2967/jnumed.120.261858 |
| Popis: | Objective: β-amyloid PET (Aβ-PET) is an important tool for quantification of amyloidosis in the brain of suspected Alzheimer's 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 non-fibrillar Aβ components to the in vivo Aβ-PET signal remain unclear. Thus, we obtained two 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 three, six and 12 months of age by longitudinal 18F-florbetaben Aβ-PET and with immunohistochemical analysis of the fibrillar and total Aβ burdens. We then applied group level inter-modality regression models using age and genotype matched sets of fibrillar/ non-fibrillar Aβ data (predictors) and Aβ-PET results (outcome) for both transgenic models. An independent group of double-hit APPPS1 mice with dysfunctional microglia due to knock-out of triggering receptor expression on myeloid cells 2 (Trem2-/-) served for validation and evaluation of translational impact. Results: Neither fibrillar nor non-fibrillar Aβ content alone sufficed to explain the Aβ-PET findings in either transgenic AD model. However, a regression model compiling fibrillar and non-fibrillar Aβ together with the estimate of individual heterogeneity and age at scanning could explain a 93% of variance of the Aβ-PET signal (P |
| Databáze: | OpenAIRE |
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