Microglial proteins Iba1 and TSPO (PBR) are differentially altered in the temporal cortex and cerebellum according to Braak stage

Garland, Emma F., Dennett, Oliver and Nicoll, James A.R. , et al. (2022) Microglial proteins Iba1 and TSPO (PBR) are differentially altered in the temporal cortex and cerebellum according to Braak stage. Alzheimer's & Dementia, 18 (S3), [e061017]. (doi:10.1002/alz.061017).

Abstract

Background: microglia are the resident immune cells in the brain and contribute to the neuropathology of Alzheimer’s disease (AD) by mechanisms not completely known. Iba1 is a microglial marker associated with homeostatic and motility functions. Whereas TSPO (PBR) is a marker of the mitochondrial membrane in microglia, macrophages and endothelial cells and is proposed to be associated with the activated subtype of microglia.

Method: to assess both Iba1 and PBR, we retrieved human temporal cortex and cerebellum samples from 57 cases at different stages of the disease, based on the Braak staging (Group 0-II n=19, Group III-IV n=20, Group V-VI n=18), using immunohistochemical analysis. Additionally, a V-Plex Mesoscale Discovery (MSD) analysis was performed to assess the inflammatory environment.

Result: there was a significant increase in PBR percentage load (P
Conclusion: this emphasises the outcome that, in AD, PBR may contribute to inflammation in the temporal cortex and Iba1 may be correlated to inflammation in the cerebellum. The findings indicate that TSPO relates to microglial activation in the brain which is Braak-stage specific and consequently supports the use of TSPO ligands for positron emission tomography (PET) imaging of Alzheimer’s disease-relevant microglial activity in vivo. Moreover, the absence of an increase in PBR load in the cerebellum could qualify this structure as a reference region for PET quantification.

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Contributors

Author: Emma F. Garland

Author: James A.R. Nicoll

Author: Delphine Boche

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