Association between brain and skull marrow metabolism in Parkinson's disease: Insights into brain-skull marrow crosstalk.

OBJECTIVES

Parkinson's disease (PD) exhibited abnormalities in skull marrow metabolism. However, the relationship between abnormal skull marrow metabolism and PD-related brain metabolic alterations remains unknown. This study aimed to investigate the relationship between brain metabolic changes and aberrant skull marrow metabolisms in PD.

METHODS

18F-fluorodeoxyglucose positron emission tomography images were acquired from 34 healthy controls (HCs), 32 prodromal PD (pPD), 50 de novo PD (dnPD) and 74 medicated PD (mPD) patients. Expression scores of PD-related patterns (PDRP) and skull marrow glucose metabolic profiles were extracted. Comparisons of glucose uptake in the brain and skull marrow was assessed among groups. The associations between brain and skull marrow glucose metabolism were also evaluated. Furthermore, cross-correlation and Granger causal analysis was used to assess the probable ordering between brain and skull marrow glucose metabolisms across different stages of PD.

RESULTS

dnPD and mPD patients exhibited elevated PDRP expression compared to HCs (p < 0.001). Similarly, clinically-confirmed PD patients experienced skull marrow hypermetabolism compared to HCs (p ≤ 0.014). PDRP and cranial glucose metabolisms showed significant associations (r = 0.15-0.17, p = 0.021-0.046). In addition, cross-correlation analysis revealed significant positive lags for the peak correlation coefficients between PDRP and skull marrow metabolisms (p < 0.05). Granger causal analysis revealed significant positive causal projections from PDRP to skull marrow metabolisms (Granger causality coefficient = 0.314-0.344, p ≤ 0.001).

INTERPRETATION: This study showed the associations between brain and skull marrow glucose metabolism in different stages of PD, which suggested brain-skull marrow signaling in PD, likely involving neuroimmune crosstalk at the brain-skull interface.