P2X<sub>7</sub>R influences tau aggregate burden in human tauopathies and shows distinct signalling in microglia and astrocytes.

Here we further show that CCL2 protein is upregulated in BA9 from AD (Braak V-VI) relative to controls (Braak 0-II), while IL-6 protein followed an increasing trend that did not reach statistical significance ( Fig. 4 k-m).

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Similarly, P2RX7 was also found among the most upregulated transcripts in the primary tauopathy progressive supranuclear palsy (PSP) relative to controls, although this did not reach statistical significance ( Fig. 1 h, Table S3 ) . 3.2 P2RX7 mRNA is expressed in astrocytes and microglia proximal to plaques in AD brain To better understand which neural cells upregulate P2X 7 R in AD, we characterised the cell-type specific localisation of P2X 7 R in the human brain, an issue that remains controversial in the field ( Illes et al., 2017 , Miras-Portugal et al., 2017 ).

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