In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. S4 ( 2020-12)
Abstract:
In vivo assessment of neuroinflammation by 18 kDa translocator protein positron‐emission‐tomography (TSPO‐PET) ligands receives growing interest in preclinical and clinical research of neurodegenerative disorders. Higher TSPO expression in females has been reported for cognitively normal humans, but such effects have not yet been evaluated in rodent models of neurodegeneration and their controls. Thus, we aimed to investigate the impact of sex on TSPO expression in amyloid and tau mouse models and wild‐type (WT). Method Longitudinal 18F‐GE‐180 TSPO‐PET ( 18 F‐GE180) data of App NL‐G‐F (amyloid model), P301S (tau model) and C57Bl/6 (WT) mice were evaluated between two and twelve months of age. App NL‐G‐F received additional longitudinal amyloid‐PET (Aβ‐PET; 18 F‐florbetaben). Immunohistochemistry also served for validation of microglial (Iba1, CD68) and tau (AT8) markers at the terminal time point. PET and immunohistochemistry were quantified in cortical regions and compared by linear mixed models (PET) and analysis of variance (immunohistochemistry) between male and female mice. Result The amyloid model App NL‐G‐F revealed a distinct cortical increase of TSPO‐PET values from 2.5 to 10 months in female mice (+31%), whereas male mice only increased slightly (+6%). The linear mixed model indicated a significant sex x time interaction (T=‐2.953, b/SE=‐0.011/0.004, p=0.0048, Figure 1A), validated by Iba1 and CD68 immunohistochemistry (Figure 2). Aβ‐PET values in the same App NL‐G‐F mice indicated no significant time x sex interaction (T=0.425, b/SE=0.001/0.003, p=0.673, Figure 3). The P301S tau model showed strong cortical increases of TSPO‐PET from 2 to 8.5 months of age (female: +32%, male: +36%) but no significant sex x time interaction (T=‐0.671, b/SE=‐0.003/0.005, p=0.504, Figure 1B) and no differences in Iba1, CD68 or AT8 were observed. TSPO‐PET values in WT mice indicated an increase with time (female: +23%, male +4%) and a significant time x sex interaction was found (T=‐4.171, b/SE=‐0.009/0.002, p 〈 0.001, Figure 1C). Conclusion Female mice indicate a sex dependent elevation of glial activation in response to amyloidosis but not to tau pathology which could be related to differences in sex dependency of microglial activation pathways in presence of both proteins. Sex requires attention when microglia activation is evaluated in mouse models of Alzheimer’s disease and requires detailed studies in human disease.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2201940-6
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