Microgliosis is part of the immunobiology of Creutzfeldt-Jakob disease (CJD). This is the first report using 11C-(R)-PK11195 PET imaging in vivo to measure 18 kDa translocator protein (TSPO) expression, indexing microglia activation, in symptomatic CJD patients, followed by a postmortem neuropathology comparison. One genetic CJD (gCJD) patient, two sporadic CJD (sCJD) patients, one variant CJD (vCJD) patient (mean ± SD age, 47.50 ± 15.95 years), and nine healthy controls (mean ± SD age, 44.00 ± 11.10 years) were included in the study. TSPO binding potentials were estimated using clustering and parametric analyses of reference regions. Statistical comparisons were run at the regional and at the voxel-wise levels. Postmortem evaluation measured scrapie prion protein (PrPSc) immunoreactivity, neuronal loss, spongiosis, astrogliosis, and microgliosis. 11C-(R)-PK11195-PET showed a significant TSPO overexpression at the cortical level in the two sCJD patients, as well as thalamic and cerebellar involvement; very limited parieto-occipital activation in the gCJD case; and significant increases at the subcortical level in the thalamus, basal ganglia, and midbrain and in the cerebellum in the vCJD brain. Along with misfolded prion deposits, neuropathology in all patients revealed neuronal loss, spongiosis and astrogliosis, and a diffuse cerebral and cerebellar microgliosis which was particularly dense in thalamic and basal ganglia structures in the vCJD brain. These findings confirm significant microgliosis in CJD, which was variably modulated in vivo and more diffuse at postmortem evaluation. Thus, TSPO overexpression in microglia activation, topography, and extent can vary in CJD subtypes, as shown in vivo, possibly related to the response to fast apoptotic processes, but reaches a large amount at the final disease course.
Iaccarino, L., Moresco, R., Presotto, L., Bugiani, O., Iannaccone, S., Giaccone, G., et al. (2018). An In Vivo 11C-(R)-PK11195 PET and In Vitro Pathology Study of Microglia Activation in Creutzfeldt-Jakob Disease. MOLECULAR NEUROBIOLOGY, 55(4), 2856-2868.
|Citazione:||Iaccarino, L., Moresco, R., Presotto, L., Bugiani, O., Iannaccone, S., Giaccone, G., et al. (2018). An In Vivo 11C-(R)-PK11195 PET and In Vitro Pathology Study of Microglia Activation in Creutzfeldt-Jakob Disease. MOLECULAR NEUROBIOLOGY, 55(4), 2856-2868.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||An In Vivo 11C-(R)-PK11195 PET and In Vitro Pathology Study of Microglia Activation in Creutzfeldt-Jakob Disease|
|Autori:||Iaccarino, L; Moresco, R; Presotto, L; Bugiani, O; Iannaccone, S; Giaccone, G; Tagliavini, F; Perani, D|
|Data di pubblicazione:||2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s12035-017-0522-6|
|Appare nelle tipologie:||01 - Articolo su rivista|