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

Abstract

Parkinson disease (PD) is identified as tremor-dominant (TD) and postural instability and gait difficulty (PIGD) phenotypes. The relationships between motor phenotypes and cognitive impairment and the underlying mechanisms relating pathological proteins and neurotransmitters in cerebrospinal fluid (CSF) are unknown. We evaluated the motor symptoms and cognitive function by scales, and detected the levels of pathological proteins and neurotransmitters in CSF. TD group and PIGD group had significantly higher levels of total tau, tau phosphorylated at the position of threonine 181(P-tau181t), threonine 231, serine 396, serine 199 and lower β amyloid (Aβ)1–42 level in CSF than those in control group; PIGD group had significantly higher P-tau181t level and lower Aβ1–42 level than those in TD group. In PD group, PIGD severity was negatively correlated with MoCA score and Aβ1–42 level in CSF, and positively correlated with Hoehn-Yahr stage and P-tau181t level in CSF. In PIGD group, PIGD severity was negatively correlated with homovanillic acid (HVA) level in CSF, and HVA level was positively correlated with Aβ1–42 level in CSF. PIGD was significantly correlated with cognitive impairment, which underlying mechanism might be involved in Aβ1–42 aggregation in brain and relevant neurochemical disturbance featured by the depletion of HVA in CSF.

Pathological Influences on Clinical Heterogeneity in Lewy Body Diseases

“…In addition, patients with a higher burden of PIGD signs have decreased survival when matched to other patients with similar age and disease duration . Patients with lower CSF Aβ and higher CSF tau (i.e., findings indicative of underlying AD copathology) are more likely to have a PIGD phenotype . One of these studies was a partial analysis of PD patients with new‐onset disease recruited to the PPMI (Parkinson Progression Markers Initiative), a project sponsored by the Michael J.…”

“…125,126 Patients with lower CSF Aβ and higher CSF tau (i.e., findings indicative of underlying AD copathology) are more likely to have a PIGD phenotype. 127,128 One of these studies was a partial analysis of PD patients with new-onset disease recruited to the PPMI (Parkinson Progression Markers Initiative), a project sponsored by the Michael J. Fox Foundation, but a subsequent analysis failed to reproduce the earlier result.…”

Influence of Energy Deficiency on the Molecular Processes ofSubstantia Nigra Pars CompactaCell for Understanding Parkinsonian Neurodegeneration: A Comprehensive Biophysical Computational Model

“…In genetics, the phenotype of an organism depends on the underlying genotype (Talbot et al, 2016). Similarly, the occurrence of different phenotypes of a disease can be driven by underlying dysfunctions occurring at different levels in the hierarchy such as molecular, cellular and systems levels (Angeli et al, 2013;Zuo et al, 2017). In PD, the loss of dopaminergic neurons in SNc results in the manifestation of PD symptoms and the cause of the SNc cell loss is still not clearly elucidated.…”

Use of Functional Magnetic Resonance Imaging to Assess How Motor Phenotypes of Parkinson’s Disease Respond to Deep Brain Stimulation

“…AR and PIGD phenotypes often have faster disease progression and dementia onset, compared to TD phenotype . Additionally, local field potentials (LFP) , GABA plasma receptors , and balance testing differ between groups . The superior subthalamic nucleus (STN) produced slow high‐frequency oscillations and beta band coupling that were found to be correlated with the TD cohort, while the inferior STN produced fast high‐frequency oscillations and beta band coupling and correlated with the PIGD cohort .…”