TY - JOUR
T1 - An in vivo 11C-PK PET study of microglia activation in Fatal Familial Insomnia
AU - Iaccarino, Leonardo
AU - Presotto, Luca
AU - Bettinardi, Valentino
AU - Gianolli, Luigi
AU - Roiter, Ignazio
AU - Capellari, Sabina
AU - Parchi, Piero
AU - Cortelli, Pietro
AU - Perani, Daniela
N1 - Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Capellari Sabina, Parchi Piero, Cortelli Pietro)
PY - 2018
Y1 - 2018
N2 - Objective: Postmortem studies reported significant microglia activation in association with neuronal apoptosis in Fatal Familial Insomnia (FFI), indicating a specific glial response, but negative evidence also exists. An in vivo study of local immune responses over FFI natural course may contribute to the understanding of the underlying pathogenesis. Methods: We included eight presymptomatic subjects (mean ± SD age:44.13 ± 3.83 years) carrying the pathogenic D178N-129met FFI mutation, one symptomatic patient (male, 45 yrs. old), and nine healthy controls (HC) (mean ± SD age: 44.00 ± 11.10 years.) for comparisons. 11C-(R)-PK11195 PET allowed the measurement of Translocator Protein (TSPO) overexpression, indexing microglia activation. A clustering algorithm was adopted to define subject-specific reference regions. Voxel-wise statistical analyses were performed on 11C-(R)-PK11195 binding potential (BP) images both at the group and individual level. Results: The D178N-129met/val FFI patient showed significant 11C-(R)-PK11195 BP increases in the midbrain, cerebellum, anterior thalamus, anterior cingulate cortex, orbitofrontal cortex, and anterior insula, bilaterally. Similar TSPO increases, but limited to limbic structures, were observed in four out of eight presymptomatic carriers. The only carrier with the codon 129met/val polymorphism was the only one showing an additional TSPO increase in the anterior thalamus. Interpretation: In comparison to nonprion neurodegenerative diseases, the observed lack of a diffuse brain TSPO overexpression in preclinical and the clinical FFI cases suggests the presence of a different microglia response. The involvement of limbic structures might indicate a role for microglia activation in these key pathologic regions, known to show the most significant neuronal loss and functional deafferentation in FFI.
AB - Objective: Postmortem studies reported significant microglia activation in association with neuronal apoptosis in Fatal Familial Insomnia (FFI), indicating a specific glial response, but negative evidence also exists. An in vivo study of local immune responses over FFI natural course may contribute to the understanding of the underlying pathogenesis. Methods: We included eight presymptomatic subjects (mean ± SD age:44.13 ± 3.83 years) carrying the pathogenic D178N-129met FFI mutation, one symptomatic patient (male, 45 yrs. old), and nine healthy controls (HC) (mean ± SD age: 44.00 ± 11.10 years.) for comparisons. 11C-(R)-PK11195 PET allowed the measurement of Translocator Protein (TSPO) overexpression, indexing microglia activation. A clustering algorithm was adopted to define subject-specific reference regions. Voxel-wise statistical analyses were performed on 11C-(R)-PK11195 binding potential (BP) images both at the group and individual level. Results: The D178N-129met/val FFI patient showed significant 11C-(R)-PK11195 BP increases in the midbrain, cerebellum, anterior thalamus, anterior cingulate cortex, orbitofrontal cortex, and anterior insula, bilaterally. Similar TSPO increases, but limited to limbic structures, were observed in four out of eight presymptomatic carriers. The only carrier with the codon 129met/val polymorphism was the only one showing an additional TSPO increase in the anterior thalamus. Interpretation: In comparison to nonprion neurodegenerative diseases, the observed lack of a diffuse brain TSPO overexpression in preclinical and the clinical FFI cases suggests the presence of a different microglia response. The involvement of limbic structures might indicate a role for microglia activation in these key pathologic regions, known to show the most significant neuronal loss and functional deafferentation in FFI.
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U2 - 10.1002/acn3.498
DO - 10.1002/acn3.498
M3 - Article
C2 - 29376088
AN - SCOPUS:85038090933
VL - 5
SP - 11
EP - 18
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
SN - 2328-9503
IS - 1
ER -