Neuroinflammation In Parkinson's Disease: A Study With [11C]PBR28 PET And Cerebrospinal Fluid Markers
Haidar Al-Abdulrasul, Riikka Ajalin, Jouni Tuisku, Henrik Zetterberg, Kaj Blennow, Tero Vahlberg, Laura Ekblad, Semi Helin, Sarita Forsback, Juha Rinne, Anna Brück
Purpose To investigate neuroinflammation in Parkinson's disease (PD) with [11C]PBR28 positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers, and the relationship to dopaminergic functioning measured with 6-[18F]-fluoro-L-dopa ([18F]FDOPA) PET. Methods The clinical cohort consisted of 20 patients with PD and 51 healthy controls (HC). All HC and 15 PD participants underwent [11C]PBR28 High Resolution Research Tomograph (HRRT) PET examination for the quantitative assessment of
... cerebral binding to the translocator protein (TSPO), a neuroinflammation marker. CSF samples were available from 17 patients with PD and 21 HC and were examined for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3-like 1 protein (YKL-40), neurogranin (NG), alpha-synuclein (aSyn) and oligo-alpha-synuclein. All patients with PD underwent [18F]FDOPA HRRT PET examination. Results Subjects with PD and HC did not differ in the total volume of distribution (VT) of [11C]PBR28 in any studied brain regions. In the CSF analyses, higher levels of sTREM2 and NG were associated with more severe motor symptoms evaluated by The Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) (p = 0.041 and p = 0.016 respectively). Additionally, in the PD group increased VT in the basal ganglia and substantia nigra (SN) were related to higher levels of YKL-40 (p < 0.01). No significant correlations were found between [11C]PBR28 VT and [18F]FDOPA uptake or between [11C]PBR28 VT and UPDRS-III in any studied region. No significant correlations were observed between the CSF markers and [18F]FDOPA uptake in the SN or the striatum. No significant correlations were found between [11C]PBR28 VT and aSyn, oligo-aSyn or their ratio. Conclusion Associations between CSF biomarkers, motor disability and [11C]PBR28 VT in the striatum and SN may support a role for neuroinflammation in PD.