Glia cells are highly dysregulated in human sCJD. Human brain tissues are usually fixed in 4% buffered formalin. To inactivate prion infectivity, tissues should be incubated in 98% formic acid for 1.5 h. Tissues from healthy human controls should be similarly treated with formic acid, to enable identical staining conditions. Frontal cortex and cerebellum brain sections from sCJD patients and control patients without neurologic disease are shown for (A) the pan-microglia/macrophage marker IBA1 and homeostatic microglia marker TMEM119 [97]. Note that while IBA1+ microglia are increased in sCJD staining, the intensity of TMEM119 staining is reduced compared to an age-matched non-demented control patient [97]. Deposits of misfolded PrPSc (sCJD) are also shown. Scale bar: 200 µm. (B) Besides microglia, astrocytes are also highly dysregulated in prion diseases such as sCJD [97,107], as displayed by the astrocyte markers GFAP and YKL-40 for an sCJD case and an age-matched control. Scale bar: 200 µm.