Amyloid beta accumulations and enhanced neuronal differentiation in cerebral organoids of Dutch-type cerebral amyloid angiopathy patients

荷兰型脑淀粉样血管病患者脑类器官中淀粉样β蛋白的积累和神经元分化增强

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作者:Elena Daoutsali, Barry A Pepers, Stavros Stamatakis, Linda M van der Graaf, Gisela M Terwindt, David A Parfitt, Ronald A M Buijsen, Willeke M C van Roon-Mom

Conclusions

These results illustrate the potential of cerebral organoids as in vitro disease model of D-CAA that can be used to understand disease mechanisms of D-CAA and can serve as therapeutic intervention platform for various Aβ-related disorders.

Methods

We generated cerebral organoids from four D-CAA patients and four controls, cultured them up to 110 days and performed immunofluorescent and targeted gene expression analyses at two time points (D52 and D110).

Results

D-CAA cerebral organoids exhibited Aβ accumulations, showed enhanced neuronal and astrocytic gene expression and TGFβ pathway de-regulation. Conclusions: These results illustrate the potential of cerebral organoids as in vitro disease model of D-CAA that can be used to understand disease mechanisms of D-CAA and can serve as therapeutic intervention platform for various Aβ-related disorders.

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