Objective: Investigate if inflammatory biomarkers moderate the association between, cholinergic basal forebrain free water fraction and cholinergic innervation in idiopathic Parkinson’s disease.

Background: The cholinergic basal forebrain (cBF) is impacted by a-synuclein in idiopathic Parkinson’s disease (PD), causing cortical cholinergic denervation in some. a-Synuclein deposition causes neuronal inflammation reflected in free water fraction (FWF), an extracellular water metric. To our knowledge, no study has examined the relationship between inflammatory biomarkers, FWF, and cholinergic levels in PD. This study aimed to 1) investigate the association between FWF and peripheral inflammatory biomarkers, and 2) determine if inflammatory biomarker levels moderate the FWF-acetylcholine association in PD.

Method: Participants included 121 individuals with PD who underwent structural and diffusion brain MRI, [¹⁸F] fluoroethoxybenzovesamicol cholinergic PET, and blood plasma analysis for high sensitivity c-reactive protein (hsCRP). 94 participants had additional blood plasma analysis for inflammatory cytokines (IL1-b, IL2, IL6, IL10, and TNF-a). Cholinergic binding was quantified across cortical and limbic regions innervated from cBF. We estimated FWF with Freewater Estimator running Interpolated Initialization. We used the cBF region of interest defined by AssemblyNet. Regression analyses examined the FWF-inflammation biomarker association. Then, for each inflammatory biomarker, we completed multiple regression analyses with FWF, biomarker levels, and the FWF x biomarker interaction as independent variables and cholinergic binding as a dependent variable. Regressions controlled for age and blood pressure.

Results: IL10 trended towards associating with CBF FWF (b=.178, p=.073). For interaction analyses, cBF FWF by hsCRP trended towards significance (b=.174, p=.059), wit a significant FWF-hsCRP in the lower third tertile (b= -.415, p=.041), but not other tertiles. No other interaction term was statistically significant.

Conclusion: Our study found no significant associations between peripheral inflammation biomarkers and cBF FWF, though the cBF FWF-acetylcholine association may be modified by inflammation reflected in hsCRP. Future investigations should examine these associations using central nervous system inflammation biomarkers, and investigate associations with individual basal forebrian nuclei.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/inflammation-biomarkers-and-free-water-fraction-in-the-cholinergic-forebrain-system-in-idiopathic-parkinsons-disease/