White matter damage and systemic inflammation in Parkinson’s disease

Abstract

BackgroundSystemic inflammation and white matter (WM) alterations have been noted as effects of Parkinson’s disease (PD). This study sought to evaluate WM integrity in PD patients using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation.MethodsSixty-six patients with PD (23 men and 43 women) and 67 healthy volunteers (29 men and 38 women) underwent blood sampling to quantify inflammatory markers and DTI scans to determine fiber integrity. The inflammatory markers included leukocyte apoptosis, as well as cellular and serum adhesion molecules, in each peripheral blood sample. DTI-related indices [including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] were derived from DTI scans. The resulting FA maps were compared using voxel-based statistics to determine differences between the PD and control groups. The differences in the DTI indices, clinical severity, and inflammatory markers were correlated.ResultsExploratory group-wise comparison between the two groups revealed that the PD patients exhibited extensive DTI index differences. Low FA accompanied by high RD and MD, without significant differences in AD, suggesting a demyelination process, were found in the parietal, occipital, cerebellar, and insular WM of the PD patients. The declined DTI indices were significantly correlated with increased clinical disease severity, adhesion molecules, and leukocyte apoptosis.ConclusionsPatients with PD experience WM integrity damage in vulnerable regions, and these impairments are associated with increased disease severity and systemic inflammation. The possible interactions among them may represent variant neuronal injuries and their consequent processes in PD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-017-0367-y) contains supplementary material, which is available to authorized users.

Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

“…Inflammatory activity drives levels of circulating pro-inflammatory cytokines, which fluctuate in response to acute insults, like infection or injury, and/or chronic disruptions in homeostasis and tissue function (Cohen et al, 2012;Gouin, Glaser, Malarkey, Beversdorf, & Kiecolt-Glaser, 2012;Hotamisligil, 2017;Scrivo, Vasile, Bartosiewicz, & Valesini, 2011). This gives inflammatory processes wide berth to impact brain structure, evidence of which is reflected in both early development and adulthood (Bettcher et al, 2013(Bettcher et al, , 2014Favrais et al, 2011;Jiang, Cowan, Moonah, & Petri Jr., 2018;Lim et al, 2013;Rasmussen et al, 2018) and in health and illness (Benedetti et al, 2016;Chiang et al, 2017;Najjar & Pearlman, 2015;Prasad et al, 2015;Yadav et al, 2010). Our study aimed to evaluate common genetic influences on white matter microstructure, as measured by DTI, and markers of inflammation, as measured by circulating proinflammatory cytokines in humans.…”

“…In adulthood, higher levels of circulating cytokines are also associated with lower FA values along with age-related cognitive decline (Bettcher et al, 2014;Lim, Krajina, & Marsland, 2013). Furthermore, increased circulating levels of proinflammatory cytokines are associated with reduced FA in several disorders including schizophrenia (Najjar & Pearlman, 2015;Prasad, Upton, Nimgaonkar, & Keshavan, 2015), bipolar disorder (Benedetti et al, 2016), Parkinson's disease (Chiang et al, 2017), lipid metabolism disorders (Ryan et al, 2017), and tuberculosis meningitis (Yadav et al, 2010), possibly indicating joint impacts on a variety of illnesses.…”

Role of the combination of FA and parameters as a new diagnostic method in therapeutic evaluation of parkinson's disease

“…7 Furthermore, Chiang et al found that a low FA value was accompanied by high mean diffusivity (MD) in the parietal, occipital, and cerebellar regions in patients with PD, which was indicative of demyelination in these areas, and that FA values were significantly positively correlated with disease severity. 9 Furthermore, the T Ã 2 parameter, sensitive to the macroscopic and microscopic inhomogeneities of the magnetic field, could also serve as a new biomarker in PD diagnosis. [10][11][12] In a recent 6-OHDA rat model study, Olmedo-Diaz et al found that iron inclusions were closely associated with active microglia, indicating a role for microglia in brain iron accumulation and dopamine neurodegeneration.…”

“…For example, Yoshikawa et al found that the FA value in the region of the SN in the thalamus/caudate nucleus complex decreased markedly in patients with PD . Furthermore, Chiang et al found that a low FA value was accompanied by high mean diffusivity (MD) in the parietal, occipital, and cerebellar regions in patients with PD, which was indicative of demyelination in these areas, and that FA values were significantly positively correlated with disease severity . Furthermore, the parameter, sensitive to the macroscopic and microscopic inhomogeneities of the magnetic field, could also serve as a new biomarker in PD diagnosis .…”

Associations among Cognitive Functions, Plasma DNA, and Diffusion tensor image along the perivascular space (DTI-ALPS) in Patients with Parkinson's Disease

“…Increased plasma DNA level may support the existence of a critical primary pathophysiology of PD, specifically abnormal systemic oxidative stress and the acceleration of peripheral immune cell infiltration into the brain. Systemic inflammation involving various pathways, such as BBB dysfunction and the infiltration of peripheral immune cells and circulating cytokines have been widely reported in PD [18][19][20]. Of note, BBB disruption and inflammation are actually connected in a vicious cycle.…”