Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Parkinson’s disease.
Title: Mapping brain structural differences and neuroreceptor correlates in Parkinson's disease visual hallucinations
Authors: Miriam Vignando, Dominic ffytche, Simon J. G. Lewis, Phil Hyu Lee, Seok Jong Chung, Rimona S. Weil, Michele T. Hu, Clare E. Mackay, Ludovica Griffanti, Delphine Pins, Kathy Dujardin, Renaud Jardri, John-Paul Taylor, Michael Firbank, Grainne McAlonan, Henry K. F. Mak, Shu Leong Ho, Mitul A. Mehta
Type: Article of Nature Communications
Parkinson’s psychosis (PDP) describes a spectrum of symptoms that may arise in Parkinson’s disease (PD) including visual hallucinations (VH). Imaging studies investigating the neural correlates of PDP have been inconsistent in their findings, due to differences in study design and limitations of scale. Here we use empirical Bayes harmonisation to pool together structural imaging data from multiple research groups into a large-scale mega-analysis, allowing us to identify cortical regions and networks involved in VH and their relation to receptor binding. Differences of morphometrics analysed show a wider cortical involvement underlying VH than previously recognised, including primary visual cortex and surrounding regions, and the hippocampus, independent of its role in cognitive decline. Structural covariance analyses point to the involvement of the attentional control networks in PD-VH, while associations with receptor density maps suggest neurotransmitter loss may be linked to the cortical changes.
Access this article: https://doi.org/10.1038/s41467-022-28087-0
Title: Early auditory responses to speech sounds in Parkinson’s disease: preliminary data
Authors: Fatemeh Mollaei, Douglas M. Shiller, Shari R. Baum, Vincent L. Gracco
Type: Article of Scientific Reports
Parkinson’s disease (PD), as a manifestation of basal ganglia dysfunction, is associated with a number of speech deficits, including reduced voice modulation and vocal output. Interestingly, previous work has shown that participants with PD show an increased feedback-driven motor response to unexpected fundamental frequency perturbations during speech production, and a heightened ability to detect differences in vocal pitch relative to control participants. Here, we explored one possible contributor to these enhanced responses. We recorded the frequency-following auditory brainstem response (FFR) to repetitions of the speech syllable [da] in PD and control participants. Participants with PD displayed a larger amplitude FFR related to the fundamental frequency of speech stimuli relative to the control group. The current preliminary results suggest the dysfunction of the basal ganglia in PD contributes to the early stage of auditory processing and may reflect one component of a broader sensorimotor processing impairment associated with the disease.
Access this article: https://doi.org/10.1038/s41598-022-05128-8
Title: Metabolite and lipoprotein profiles reveal sex-related oxidative stress imbalance in de novo drug-naive Parkinson’s disease patients
Authors: Gaia Meoni, Leonardo Tenori, Sebastian Schade, Cristina Licari, Chiara Pirazzini, Maria Giulia Bacalini, Paolo Garagnani, Paola Turano, PROPAG-AGEING Consortium, Claudia Trenkwalder, Claudio Franceschi, Brit Mollenhauer, Claudio Luchinat
Type: Article of npj Parkinson’s Disease
Parkinson’s disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress.
Access this article: https://doi.org/10.1038/s41531-021-00274-8
Title: Magnetoencephalography detects phase-amplitude coupling in Parkinson’s disease
Authors: Masataka Tanaka, Takufumi Yanagisawa, Ryohei Fukuma, Naoki Tani, Satoru Oshino, Masahito Mihara, Noriaki Hattori, Yuta Kajiyama, Ryota Hashimoto, Manabu Ikeda, Hideki Mochizuki, Haruhiko Kishima
Type: Article of Scientific Reports
To characterize Parkinson’s disease, abnormal phase-amplitude coupling is assessed in the cortico-basal circuit using invasive recordings. It is unknown whether the same phenomenon might be found in regions other than the cortico-basal ganglia circuit. We hypothesized that using magnetoencephalography to assess phase-amplitude coupling in the whole brain can characterize Parkinson’s disease. We recorded resting-state magnetoencephalographic signals in patients with Parkinson’s disease and in healthy age- and sex-matched participants. We compared whole-brain signals from the two groups, evaluating the power spectra of 3 frequency bands (alpha, 8–12 Hz; beta, 13–25 Hz; gamma, 50–100 Hz) and the coupling between gamma amplitude and alpha or beta phases. Patients with Parkinson’s disease showed significant beta–gamma phase-amplitude coupling that was widely distributed in the sensorimotor, occipital, and temporal cortices; healthy participants showed such coupling only in parts of the somatosensory and temporal cortices. Moreover, beta- and gamma-band power differed significantly between participants in the two groups (P < 0.05). Finally, beta–gamma phase-amplitude coupling in the sensorimotor cortices correlated significantly with motor symptoms of Parkinson’s disease (P < 0.05); beta- and gamma-band power did not. We thus demonstrated that beta–gamma phase-amplitude coupling in the resting state characterizes Parkinson's disease.
Access this article: https://doi.org/10.1038/s41598-022-05901-9
Title: Insulin-like growth factor 2 and autophagy gene expression alteration arise as potential biomarkers in Parkinson’s disease
Authors: Denisse Sepúlveda, Felipe Grunenwald, Alvaro Vidal, Paulina Troncoso-Escudero, Marisol Cisternas-Olmedo, Roque Villagra, Pedro Vergara, Carlos Aguilera, Melissa Nassif, Rene L. Vidal
Type: Article of Scientific Reports
Insulin-like growth factor 2 (IGF2) and autophagy-related genes have been proposed as biomolecules of interest related to idiopathic Parkinson’s disease (PD). The objective of this study was to determine the IGF2 and IGF1 levels in plasma and peripheral blood mononuclear cells (PBMCs) from patients with moderately advanced PD and explore the potential correlation with autophagy-related genes in the same blood samples. IGF1 and IGF2 levels in patients’ plasma were measured by ELISA, and the IGF2 expression levels were determined by real-time PCR and Western blot in PBMCs. The expression of autophagy-related genes was evaluated by real-time PCR. The results show a significant decrease in IGF2 plasma levels in PD patients compared with a healthy control group. We also report a dramatic decrease in IGF2 mRNA and protein levels in PBMCs from PD patients. In addition, we observed a downregulation of key components of the initial stages of the autophagy process. Although IGF2 levels were not directly correlated with disease severity, we found a correlation between its levels and autophagy gene profile expression in a sex-dependent pattern from the same samples. To further explore this correlation, we treated mice macrophages cell culture with α-synuclein and IGF2. While α-synuclein treatment decreased levels Atg5, IGF2 treatment reverted these effects, increasing Atg5 and Beclin1 levels. Our results suggest a relationship between IGF2 levels and the autophagy process in PD and their potential application as multi-biomarkers to determine PD patients’ stages of the disease.
Access this article: https://doi.org/10.1038/s41598-022-05941-1
Title: Lamina-specific immunohistochemical signatures in the olfactory bulb of healthy, Alzheimer’s and Parkinson’s disease patients
Authors: Helen C. Murray, Kory Johnson, Andrea Sedlock, Blake Highet, Birger Victor Dieriks, Praju Vikas Anekal, Richard L. M. Faull, Maurice A. Curtis, Alan Koretsky, Dragan Maric
Type: Article of Communications Biology
Traditional neuroanatomy immunohistology studies involve low-content analyses of a few antibodies of interest, typically applied and compared across sequential tissue sections. The efficiency, consistency, and ultimate insights of these studies can be substantially improved using high-plex immunofluorescence labelling on a single tissue section to allow direct comparison of many markers. Here we present an expanded and efficient multiplexed fluorescence-based immunohistochemistry (MP-IHC) approach that improves throughput with sequential labelling of up to 10 antibodies per cycle, with no limitation on the number of cycles, and maintains versatility and accessibility by using readily available commercial reagents and standard epifluorescence microscopy imaging. We demonstrate this approach by cumulatively screening up to 100 markers on formalin-fixed paraffin-embedded sections of human olfactory bulb sourced from neurologically normal (no significant pathology), Alzheimer’s (AD), and Parkinson’s disease (PD) patients. This brain region is involved early in the symptomology and pathophysiology of AD and PD. We also developed a spatial pixel bin analysis approach for unsupervised analysis of the high-content anatomical information from large tissue sections. Here, we present a comprehensive immunohistological characterisation of human olfactory bulb anatomy and a summary of differentially expressed biomarkers in AD and PD using the MP-IHC labelling and spatial protein analysis pipeline.
Access this article: https://doi.org/10.1038/s42003-022-03032-5