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Title: Imaging of neuroinflammation in adult Niemann-Pick type C disease: A cross-sectional study.
Austin Authors: Walterfang, Mark;Di Biase, Maria A;Cropley, Vanessa L;Scott, Andrew M ;O'Keefe, Graeme J;Velakoulis, Dennis;Pathmaraj, Kunthi ;Ackermann, Uwe ;Pantelis, Christos
Affiliation: From the Neuropsychiatry Unit (M.W., D.V.), Royal Melbourne Hospital; Melbourne Neuropsychiatry Centre (M.W., M.A.D., V.L.C., D.V., C.P.), The University of Melbourne & North Western Mental Health; The Florey Institute of Neuroscience and Mental Health (M.W., C.P.), Department of Psychiatry (M.W., M.A.D., V.L.C., D.V., C.P.), and Centre for Neural Engineering, Department of Electrical and Electronic Engineering (C.P.), The University of Melbourne; Department of Molecular Imaging and Therapy (A.M.S., G.O., K.P., U.A.), Austin Health and The University of Melbourne, Heidelberg; Olivia Newton John Cancer Centre and La Trobe University (A.M.S., G.O., U.A.), Melbourne; and Cooperative Centre for Mental Health Research (C.P.), Carlton, Australia
Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Issue Date: 24-Mar-2020 2020
Publication information: Neurology 2020; online first: 24 March
Abstract: To test the hypothesis that neuroinflammation is a key process in adult Niemann-Pick type C (NPC) disease, we undertook PET scanning utilizing a ligand binding activated microglia on 9 patients and 9 age- and sex-matched controls. We scanned all participants with the PET radioligand 11C-(R)-PK-11195 and undertook structural MRI to measure gray matter volume and white matter fractional anisotropy (FA). We found increased binding of 11C-(R)-PK-11195 in total white matter compared to controls (p < 0.01), but not in gray matter regions, and this did not correlate with illness severity or duration. Gray matter was reduced in the thalamus (p < 0.0001) in patients, who also showed widespread reductions in FA across the brain compared to controls (p < 0.001). A significant correlation between 11C-(R)-PK11195 binding and FA was shown (p = 0.002), driven by the NPC patient group. Our findings suggest that neuroinflammation-particularly in white matter-may underpin some structural and degenerative changes in patients with NPC.
DOI: 10.1212/WNL.0000000000009287
ORCID: 0000-0002-1389-3691
PubMed URL: 32209649
Type: Journal Article
Appears in Collections:Journal articles

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