The Challenge and Opportunity to Diagnose Parkinson's Disease in Midlife

Abstract

Parkinson's disease (PD) is the most common neurodegenerative movement disorder that affects extensive regions of the nervous system. Its current clinical diagnosis is based on motor symptoms that appear late during disease progression when substantial proportions of the nigrostriatal dopaminergic neuron population are lost already. Although disturbances in sleep and other biofunctions often surface years prior to motor impairments and point to a long prodromal phase, these phenotypic signs in a person's midlife lack predictive power. They do, however, signal the unfolding of the disease and suggest molecular correlates that begin deviating early on. Revealing such trajectories, hence, promises not only a better understanding of prodromal PD but may also enable a much-needed earlier diagnosis. A nexus that may harbor such molecular trajectories is the epigenome as key etiological factors of PD-genetics, age, and environment-influence this substrate. An earlier diagnosis would also allow earlier interventions and lifestyle adjustments to improve brain function and reduce symptoms. In this review, we describe the challenges of diagnosing PD early on and highlight the opportunities that may arise from steering research efforts towards comprehensive interrogations of molecular layers during the long-time neglected midlife phase. In particular, we emphasize how existing cohorts of at-risk individuals, available animal models, and suitable markers may come together and aid in revealing molecular trajectories that offer diagnostic utility for PD in its prodromal stage.

Gut brain axis: an insight into microbiota role in Parkinson’s disease

“…Other cardinal signs of PD include bradykinesia and rigidity. As PD progresses, alphasynuclein accumulation becomes more widespread in the brain., In the past 10-20 years, the non-motor manifestations of PD have been given considerable attention (Kilzheimer et al 2019;Getz and Levin 2017).…”

“…LRRK2 PD is heterogeneous with respect to the progression and occurrence of nonmotor symptoms. On the other hand, PD associated with alpha-synuclein (SNCA) mutation is early-onset, moderately responses to levodopa treatment, progresses rapidly, where psychiatric symptom manifestations and cognitive decline are evident (Kilzheimer et al 2019;Tysnes and Storstein 2017). Another crucial factor to consider when we try to understand PD is the gene-environment interactions.…”

Thioredoxin‐1 regulates calcium homeostasis in MPP+/MPTP‐induced Parkinson's disease models

“…Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by resting tremor, bradykinesia, rigidity, and postural instability resulting from severe loss of dopaminergic (DA) neurons in the substantia nigra pars compacta region (SNpc) (Jankovic & Tan, 2020; Kilzheimer et al, 2019; Liu et al, 2019). The mechanism on PD is very complicated, and there are no effective treatments on PD until now.…”

Parkinson’s Disease: Available Clinical and Promising Omics Tests for Diagnostics, Disease Risk Assessment, and Pharmacotherapy Personalization

“…Almost all PD's biomarkers are considered of use for the diagnostics of early and premotor stages of the disease. However, it should be noted that none of these indicators itself provides comprehensive diagnostic information, and they do not allow the prognosis of the disease to be fully assessed or the diagnosis verified [16].…”