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- W2896874118 abstract "The choroid plexus (CP), consisting mainly of tightly connected choroid plexus epithelial cells (CPE) cells surrounding fenestrated capillaries is a complex structure localized in the ventricles of the brain. These CPE cells form the blood-cerebrospinal fluid barrier, which plays a vital role in the maintenance of brain homeostasis. During Alzheimer's disease (AD) several CPE related processes are severely affected (Brkic, 2015) and increasing evidence indicates that CP-derived exosomes play an important role in AD pathology. In this study we characterized the morphological alterations of the CPE cells and investigated the subcellular localization and quantification of multivesicular bodies (MVBs) and intraluminal vesicles (ILVs) in different AD mouse models by transmission electron microscopy (TEM) and 3D-scanning electron microscopy (3D-SEM). CP tissue was isolated from APP/PS1wt/wt and APP/PS1tg/wt mice at different timepoints (age 10w, 20w, 30w and 40w), and from C57Bl6/J mice intracerebroventricular (icv) injected with soluble Aβ oligomers (AβO). Isolated CP was processed for TEM and volume-EM imaging as previously described in (Balusu, 2016; Kremer, 2015). Visualization of the samples was done using a TEM (JEOL) and FIB-SEM (Zeiss Auriga FIB-SEM, Zeiss). Manual segmentation of volume-EM images was performed using Microscopy Image Browser (Belevich, 2016). 3D reconstructions were done using Imaris (Bitplane). In APP/PS1tg/wt morphological alterations of the CP are visible at the age of 20 weeks, the ultrastructure is damaged. The CPE cells lose their typical cuboidal shape, are more point-shaped, the cytoplasm becomes more translucent, the nuclei are irregularly shaped and the mitochondria are more condensed. All these changes become increasingly prominent as these mice age. In APP/PS1wt/wt mice, the same morphological alterations of the CP become only visible after 30 weeks of age. Early during disease progression (10 w), we observed higher levels of ILVs in the CP of APP/PS1tg/wt compared to age-matched APP/PS1wt/wt mice, while levels normalized at later stages. Ultrastructural changes of the CP epithelium are present in different AD models, induced by AβO. Furthermore, we observed differences in levels of ILVs in the CP early during disease progression. Further research will be necessary to evaluate the role of the CP and ILVs in AD pathology." @default.
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- W2896874118 date "2018-07-01" @default.
- W2896874118 modified "2023-10-14" @default.
- W2896874118 title "P1‐180: AN ULTRASTRUCTURAL STUDY OF THE MORPHOLOGICAL ALTERATIONS OF THE CHOROID PLEXUS EPITHELIUM IN ALZHEIMER'S DISEASE" @default.
- W2896874118 doi "https://doi.org/10.1016/j.jalz.2018.06.184" @default.
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