Potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment: a cross-sectional study

Abstract

BackgroundCognitive impairment strikingly reduces the quality of life of Parkinson’s disease (PD) patients. Studies find that pathological proteins, neuroinflammatory factors and free radicals may involve in the pathogenesis of cognitive impairment of PD, however, results are inconclusive.MethodsWe recruited 62 PD patients and 31 healthy controls. PD patients were identified with cognitive impairment, including PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD) according to the diagnostic criteria for PD-MCI and PDD issued by Movement Disorder Society Task Force. The levels of pathological proteins, including β-amyloid 1–42 (Aβ1-42),Total-tau (T-tau) and phosphorelated tau (P-tau), neuroinflammatory factors,including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ) and prostaglandin E2 (PGE2), free radicals, including hydroxyl radical (·OH), hydrogen peroxide (H2O2) and nitric oxide (NO) in cerebrospinal fluid(CSF) were detected. The levels of above factors in CSF were compared among healthy controls and patients with and without cognitive impairment. Correlation analyses were performed between Montreal Cognitive Assessment (MoCA) score and the levels of above factors in CSF.ResultsT-tau level in CSF from PD-CI patients are significantly elevated comparing with those without cognitive impairment and controls (P = 0.016 and 0.004, respectively). The levels of P-tau (S396) and · OH in PD-CI patients are significantly higher than controls (P = 0.001 and 0.014, respectively). IL-6 levels in PD-CI patients are strikingly enhanced comparing with those without cognitive impairment (P = 0.005). MoCA score is negatively correlated with the levels of T-tau (r = -0.340), P-tau (S396) (r = -0.448), IL-6 (r = -0.489) and · OH (r = -0.504) in PD-CI patients.ConclusionsElevated levels of T-tau, P-tau (S396), IL-6 and · OH in CSF are significantly correlated with cognitive impairment in PD patients. This investigation may suggest the potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment.

Biomarkers for dementia and mild cognitive impairment in Parkinson's disease

“…By contrast, the data for total (t‐tau) and phosphorylated tau (p‐tau) are less consistent, with increased or unchanged levels in PDD patients. In PD‐MCI patients, there was less or similar Aß to that in PDCN patients, whereas t‐tau was higher or no different, and p‐tau was comparable in both . Interestingly, in PDND patients, low levels of Aß and a low Aß 1‐42/total tau ratio were associated with impairment in several cognitive domains or tests: attention and working memory, executive function, memory, and phonemic and semantic fluency .…”

“…Proteins involved in inflammatory processes, oxidative stress, and neuronal viability have also been investigated (Supplementary Table 1). More C‐reactive protein was found in PDD patients than in PDND and controls, and interleukin‐6 and interleukin‐1β were more elevated in PD‐MCI than in PDCN patients or controls . PD‐MCI patients also had less interferon‐γ and tumor necrosis factor α, and higher levels of nitric oxide and hydroxyl radical than controls .…”

“…More C‐reactive protein was found in PDD patients than in PDND and controls, and interleukin‐6 and interleukin‐1β were more elevated in PD‐MCI than in PDCN patients or controls . PD‐MCI patients also had less interferon‐γ and tumor necrosis factor α, and higher levels of nitric oxide and hydroxyl radical than controls . In addition, some of these proteins were associated with global cognition in PDND and PD‐MCI patients .…”

Inflammation in mild cognitive impairment due to Parkinson's disease, Lewy body disease, and Alzheimer's disease

“…28 Our findings add that there does not appear to be an overall increase in inflammation in PD-MCI. Several studies have found no significant difference in the level of cytokines in patients with PDD compared with PD and controls, and one study found that whilst some cytokines are raised in patients with PDD, some have lower levels compared with PD and controls.…”

Phenotype of postural instability/gait difficulty in Parkinson disease: relevance to cognitive impairment and mechanism relating pathological proteins and neurotransmitters

“…However, all of the studies recruited a “pure” population, either drug-naïve patients or demented patients, who were not quite appropriate for clinical distribution of PD patients. We previously reported that the levels of total tau (T-tau) and tau phosphorylated at the position of serine 396 (P-tau396s) in CSF from PD patients with mild cognitive impairment (MCI) were negatively correlated with MoCA score15. One study found increased T-tau level in CSF of PDD patients16.…”