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Abstract
Objective 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.
Method 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).
Results 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.
Conclusions Our findings suggest that neuroinflammation—particularly in white matter—may underpin some structural and degenerative changes in patients with NPC.
Glossary
- AAL=
- automated anatomical labeling atlas;
- BMI=
- body mass index;
- CAT12=
- computational anatomy toolbox;
- FA=
- fractional anisotropy;
- FAST=
- FMRIB automated segmentation tool;
- FDR=
- false discovery rate;
- FLIRT=
- FMRIB linear image registration tool;
- FNIRT=
- FMRIB nonlinear image registration tool;
- FSL=
- FMRIB Software Library;
- IL=
- interleukin;
- MNI=
- Montreal Neurologic Institute;
- NPC=
- Niemann-Pick disease type C;
- ROI=
- region of interest;
- SCID=
- Structured Clinical Interview for DSM-IV Axis I Disorders;
- SRTM=
- simplified reference tissue model;
- TSPO=
- translocator protein;
- VBM=
- voxel-based morphometry
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received June 9, 2019.
- Accepted in final form November 5, 2019.
- © 2020 American Academy of Neurology
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