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.
Neurology. 2020 Apr 21;94(16):e1716-e1725. doi: 10.1212/WNL.0000000000009287. Epub 2020 Mar 24.
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 C-(R)-PK-11195 and undertook structural MRI to measure gray matter volume and white matter fractional anisotropy (FA).
We found increased binding of C-(R)-PK-11195 in total white matter compared to controls ( < 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 ( < 0.0001) in patients, who also showed widespread reductions in FA across the brain compared to controls ( < 0.001). A significant correlation between C-(R)-PK11195 binding and FA was shown ( = 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.
为了验证神经炎症是成年尼曼-匹克 C 型（NPC）疾病的关键过程这一假说，我们对 9 名患者和 9 名年龄和性别匹配的对照者进行了利用配体结合激活小胶质细胞的 PET 扫描。
我们对所有参与者进行了 C-（R）-PK-11195 的 PET 扫描，并进行了结构 MRI 以测量灰质体积和白质各向异性分数（FA）。
与对照组相比，我们发现患者的全白质中 C-（R）-PK-11195 的结合增加（<0.01），但灰质区域没有增加，且与疾病严重程度或病程无关。与对照组相比，患者的丘脑灰质减少（<0.0001），且大脑的 FA 广泛减少（<0.001）。患者组的 C-（R）-PK11195 结合与 FA 之间存在显著相关性（=0.002）。
我们的研究结果表明，神经炎症，特别是白质中的神经炎症，可能是 NPC 患者出现一些结构和退行性变化的原因。
