Publications by authors named "Pascal Derkinderen"

100 Publications

LeSCoD: a new clinical scale for the detection of Lewy body disease in neurocognitive disorders.

J Neurol 2021 Apr 8. Epub 2021 Apr 8.

Centre Mémoire Ressource et Recherche (CMRR), Department of Neurology, CHU Nantes, 44093, Nantes, France.

Background: Dementia with Lewy bodies remains underdiagnosed in clinical practice mainly because of the low sensitivity of existing diagnostic criteria and a strong overlap with Alzheimer's pathology that can mask the Lewy phenotype.

Objective: The objective of this study was therefore to develop and validate a new clinical scale designed to detect signs of Lewy body disease, called LeSCoD for Lewy body Screening scale in Cognitive Disorders.

Methods: 128 patients who fulfilled the clinical criteria of dementia with Lewy bodies (DLB; n = 32), Alzheimer's disease (AD; n = 77) or both (n = 19) was prospectively enrolled. F-DOPA PET imaging and/or CSF biomarkers were available in some patients. LeSCoD scale was systematically administered and the potential correlation with F-DOPA PET imaging was evaluated in a subgroup of patients.

Results: LeSCoD scale showed robust internal and external validity. We determined a cut-off of 10 above which the sensitivity and specificity for Lewy body disease diagnosis were 86% and 95%, respectively. The LeSCoD scale correlated with striatal dopamine uptake in F-DOPA PET.

Conclusion: LeSCoD scale is a simple and reliable tool for the evaluation of Lewy body disease in routine clinical practice, with a higher sensitivity and specificity than the existing criteria. It might be an alternative to the use of dopamine-specific imaging.
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http://dx.doi.org/10.1007/s00415-021-10539-0DOI Listing
April 2021

Tau in the gut, does it really matter?

J Neurochem 2021 Feb 11. Epub 2021 Feb 11.

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.

The enteric nervous system plays a critical role in the regulation of gastrointestinal tract functions and is often referred to as the 'second brain' because it shares many features with the central nervous system. These similarities include among others a large panel of neurotransmitters, a large population of glial cells and a susceptibility to neurodegeneration. This close homology between the central and enteric nervous systems suggests that a disease process affecting the central nervous system could also involve its enteric counterpart. This was already documented in Parkinson's disease, the most common synucleinopathy, in which alpha-synuclein deposits are reported in the enteric nervous system in the vast majority of patients. Tau is another key protein involved in neurodegenerative disorders of the brain. Whether changes in tau also occur in the enteric nervous system during gut or brain disorders has just begun to be explored. The scope of the present article is therefore to review existing studies on the expression and phosphorylation pattern of tau in the enteric nervous system under physiological and pathological conditions and to discuss the possible occurrence of 'enteric tauopathies'.
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http://dx.doi.org/10.1111/jnc.15320DOI Listing
February 2021

Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung's disease.

Sci Rep 2020 12 10;10(1):21725. Epub 2020 Dec 10.

University of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France.

In Hirschsprung's disease (HSCR), postoperative course remains unpredictable. Our aim was to define predictive factors of the main postoperative complications: obstructive symptoms (OS) and Hirschsprung-associated enterocolitis (HAEC). In this prospective multicentre cohort study, samples of resected bowel were collected at time of surgery in 18 neonates with short-segment HSCR in tertiary care hospitals. OS and HAEC were noted during postoperative follow-up. We assessed the enteric nervous system and the intestinal epithelial barrier (IEB) in ganglionic segments by combining immunohistochemical, proteomic and transcriptomic approaches, with functional ex vivo analysis of motility and para/transcellular permeability. Ten HSCR patients presented postoperative complications (median follow-up 23.5 months): 6 OS, 4 HAEC (2 with OS), 2 diarrhoea (without OS/HAEC). Immunohistochemical analysis showed a significant 41% and 60% decrease in median number of nNOS-IR myenteric neurons per ganglion in HSCR with OS as compared to HSCR with HAEC/diarrhoea (without OS) and HSCR without complications (p = 0.0095; p = 0.002, respectively). Paracellular and transcellular permeability was significantly increased in HSCR with HAEC as compared to HSCR with OS/diarrhoea without HAEC (p = 0.016; p = 0.009) and HSCR without complications (p = 0.029; p = 0.017). This pilot study supports the hypothesis that modulating neuronal phenotype and enhancing IEB permeability may treat or prevent postoperative complications in HSCR.
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http://dx.doi.org/10.1038/s41598-020-78340-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729910PMC
December 2020

Upregulation of enteric alpha-synuclein as a possible link between inflammatory bowel disease and Parkinson's disease.

Gut 2020 Nov 17. Epub 2020 Nov 17.

Université de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France.

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http://dx.doi.org/10.1136/gutjnl-2020-323482DOI Listing
November 2020

Correction to: Excessive buccal saliva in patients with Parkinson's disease of the French COPARK cohort.

J Neural Transm (Vienna) 2020 Oct 21. Epub 2020 Oct 21.

Biomedical Research Center, Interamerican Open University (CAECIHS-UAI), National Research Council (CONICET), Buenos Aires, Argentina.

The original version of this article unfortunately contained a mistake in Fig. 2 caption.
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http://dx.doi.org/10.1007/s00702-020-02264-1DOI Listing
October 2020

Excessive buccal saliva in patients with Parkinson's disease of the French COPARK cohort.

J Neural Transm (Vienna) 2020 12 2;127(12):1607-1617. Epub 2020 Sep 2.

Biomedical Research Center, Interamerican Open University (CAECIHS-UAI), National Research Council (CONICET), Buenos Aires, Argentina.

We describe excessive buccal saliva (EBS) prevalence in patients with Parkinson's Disease (PD) and controls of the COPARK study, its changes between "ON" and OFF" conditions and over time, its impact on Health-related Quality of life (HRQoL), and factors associated with this condition. We studied 671 ambulatory PD patients and 177 age/sex-matched controls. We defined "sialorrhea" as UPDRS item #6 (salivation) = 1 or 2; and "drooling" as item #6 = 3 or 4. SCOPA-Aut drooling score (item #2) was also available in a subset (45%) of the cohort. HRQoL was assessed by the PDQ-39 and SF-36 scales. Twenty-four months' follow-up data were available in 401/671 patients. EBS as assessed by UPDRS was present in 38% of PD patients in the "ON" condition ("Sialorrhea": 35%; "drooling": 3%). There were also more PD patients reporting "drooling" than controls according to the SCOPA-Aut (49% vs 19%, p < 0.01). UPDRS salivation score was worse in the "OFF" vs "ON" condition in PD patients with motor fluctuations (0.90 ± 0.94 vs 0.54 ± 0.79, p < 0.01). UPDRS salivation score worsened after ~ 24 months of follow-up (0.47 ± 0.70 vs 0.64 ± 0.81, p < 0.01). Worse PDQ-39 scores were observed in PD patients with EBS in bivariate but not in multivariate analyses. EBS was directly related to PD duration and severity, male gender, dysphagia, hypomimia, and autonomic dysfunction (logistic regression). EBS was more frequent in PD patients than controls, worsened in the "OFF" condition and after ~ 24 months of follow-up, moderately affected HRQoL, and was correlated with indices of bradykinesia, dysphagia, and autonomic dysfunction.
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http://dx.doi.org/10.1007/s00702-020-02249-0DOI Listing
December 2020

Tau accumulates in Crohn's disease gut.

FASEB J 2020 07 21;34(7):9285-9296. Epub 2020 May 21.

Inserm, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Université de Nantes, Nantes, France.

A sizeable body of evidence has recently emerged to suggest that gastrointestinal (GI) inflammation might be involved in the development of Parkinson's disease (PD). There is now strong epidemiological and genetical evidence linking PD to inflammatory bowel diseases and we recently demonstrated that the neuronal protein alpha-synuclein, which is critically involved in PD pathophysiology, is upregulated in inflamed segments of Crohn's colon. The microtubule associated protein tau is another neuronal protein critically involved in neurodegenerative disorders but, in contrast to alpha-synuclein, no data are available about its expression and phosphorylation patterns in inflammatory bowel diseases. Here, we examined the expression levels of tau isoforms, their phosphorylation profile and truncation in colon biopsy specimens from 16 Crohn's disease (CD) and 6 ulcerative colitis (UC) patients and compared them to samples from 16 controls. Additional experiments were performed in full thickness segments of colon of five CD and five control subjects, in primary cultures of rat enteric neurons and in nuclear factor erythroid 2-related factor (Nrf2) knockout mice. Our results show the upregulation of two main human tau isoforms in the enteric nervous system (ENS) in CD but not in UC. This upregulation was not transcriptionally regulated but instead likely resulted from a decrease in protein clearance via an Nrf2 pathway. Our findings, which provide the first detailed characterization of tau in CD, suggest that the key proteins involved in neurodegenerative disorders such as alpha-synuclein and tau, might also play a role in CD.
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http://dx.doi.org/10.1096/fj.202000414RDOI Listing
July 2020

Non-lesional status epilepticus in a patient with coronavirus disease 2019.

Clin Neurophysiol 2020 08 13;131(8):2059-2061. Epub 2020 May 13.

INSERM U1235 - The Enteric Nervous System in Gut and Brain Disorders, Nantes, France; CHU Nantes, Dept. of Neurology, University Hospital, Nantes, France.

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http://dx.doi.org/10.1016/j.clinph.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217773PMC
August 2020

Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates.

Brain 2020 05;143(5):1462-1475

University of Bordeaux, Neurodegenerative Diseases Institute, UMR 5293, F-33000 Bordeaux, France.

In Parkinson's disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the CNS. Here, we compare, in baboon monkeys, the pathological consequences of either intrastriatal or enteric injection of α-synuclein-containing Lewy body extracts from patients with Parkinson's disease. This study shows that patient-derived α-synuclein aggregates are able to induce nigrostriatal lesions and enteric nervous system pathology after either enteric or striatal injection in a non-human primate model. This finding suggests that the progression of α-synuclein pathology might be either caudo-rostral or rostro-caudal, varying between patients and disease subtypes. In addition, we report that α-synuclein pathological lesions were not found in the vagal nerve in our experimental setting. This study does not support the hypothesis of a transmission of α-synuclein pathology through the vagus nerve and the dorsal motor nucleus of the vagus. Instead, our results suggest a possible systemic mechanism in which the general circulation would act as a route for long-distance bidirectional transmission of endogenous α-synuclein between the enteric and the central nervous systems. Taken together, our study provides invaluable primate data exploring the role of the gut-brain axis in the initiation and propagation of Parkinson's disease pathology and should open the door to the development and testing of new therapeutic approaches aimed at interfering with the development of sporadic Parkinson's disease.
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http://dx.doi.org/10.1093/brain/awaa096DOI Listing
May 2020

Naltrexone Use in Treating Hypersexuality Induced by Dopamine Replacement Therapy: Impact of A/G Polymorphism on Its Effectiveness.

Int J Mol Sci 2020 Apr 24;21(8). Epub 2020 Apr 24.

Addictology and Psychiatry Department, CHU Nantes, 44093 Nantes, France.

Hypersexuality is a well-known adverse side effect of dopamine replacement therapy (DRT), and anti-craving drugs could be an effective therapeutic option. Our aim was to update the knowledge on this issue, particularly on the influence of an Opioid Receptor Mu 1 () genetic polymorphism. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We also analyzed a case of iatrogenic hypersexuality that occurred in a patient treated with DRT. An analysis of the gene was performed on said patient. Our search identified 597 publications, of which only 7 were included in the final data synthesis. All seven publications involved naltrexone use. Five of them were case reports. None of the publications mentioned DRT side effects, nor did they report genetic data. Regarding our case report, the introduction of naltrexone corresponded with the resolution of the patient's hypersexuality. Moreover, the patient carried the A/G genotype, which has been reported to be associated with a stronger response to naltrexone for patients with an alcohol use disorder. Although studies are inconclusive so far, naltrexone could be an interesting therapeutic option for resistant hypersexuality due to DRT. Carrying the A/G genotype could help explain a good response to treatment.
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http://dx.doi.org/10.3390/ijms21083002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215378PMC
April 2020

Utilization Patterns of Amantadine in Parkinson's Disease Patients Enrolled in the French COPARK Study.

Drugs Aging 2020 03;37(3):215-223

Institute of Cardiology Research, University of Buenos Aires, National Research Council (CONICET-ININCA), Buenos Aires, Argentina.

Introduction: Immediate-release (IR) amantadine has been marketed for Parkinson's disease (PD) therapy for 50 years, while two novel extended-release formulations have only recently reached the market in the US.

Objectives: The aim of this study was to describe amantadine IR utilization patterns in the French COPARK cohort, at baseline and after 2 years of follow-up.

Methods: Overall, 683 PD patients from the COPARK survey were evaluated. All patients were assessed in a standardized manner (demographics, treatments, Unified Parkinson's Disease Rating Scale [UPDRS], Hospital Anxiety and Depression Scale, Pittsburg Questionnaire and health-related quality-of-life scales (Short Form-36 [SF-36], 39-item Parkinson's Disease Questionnaire [PDQ-39]). Longitudinal data were only available for 401/683 patients (59%) with a median (P25-75) follow-up period of 23 months (18-31). Patients were assessed in the same way as in the baseline visit.

Results: At baseline, amantadine was prescribed to 61/683 (9%) patients (median dose 200 mg/day, range 100-300 mg/day). Amantadine was initiated after a median of 7 years from PD diagnosis, and its prescription was correlated with the presence of dyskinesia (logistic regression odds ratio [OR] 3.72, 95% confidence interval [CI] 1.95-7.08) and hallucinations (UPDRS I.2) [OR 1.57, 95% CI 1.08-2.29]. After 2 years, the amantadine prescription increased from 33 (8%) patients at baseline to 54 (14%) patients in the subset of 401 patients analysed twice (p = 0.001). Among the 33 patients receiving amantadine at baseline, 9 (27%) stopped amantadine, 5 (15%) increased the dose, 6 (18%) reduced the dose and 13 (40%) stayed at the same doses. Treatment was initiated in 30/54 new patients (55%). Patients who started amantadine or increased its dose (n = 35) had more levodopa-induced dyskinesias at baseline (OR 7.02, 95% CI 3.09-15.90) and higher Mini-Mental State Examination score at follow-up (OR 1.37, 95% CI 1.06-1.79). Undergoing deep brain stimulation was related to stopping or downtitrating amantadine (OR 22.02, 95% CI 4.24-114.44; n = 15).

Conclusions: In this cohort, amantadine was used in 10% of patients. Its use increased during follow-up, despite the fact that one-third of patients who received amantadine at baseline stopped taking it. Amantadine prescription was mainly correlated with the presence of dyskinesia.
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http://dx.doi.org/10.1007/s40266-019-00740-2DOI Listing
March 2020

The gut in Parkinson's disease: Bottom-up, top-down, or neither?

Neurogastroenterol Motil 2020 01;32(1):e13777

DistAlz, Licend, CHU Lille, INSERM URM_S1172, University Lille, Lille, France.

The gut-brain axis is a hot topic in Parkinson's disease. In an attempt to decipher its role in the disease pathogenesis, several animal models have been developed. Most of these models tried to reproduce Braak's hypothesis by showing that the pathological process could spread from the gut to the brain (bottom-up scenario). Interestingly, others groups showed that a top-down scenario could also occur and that 6-hydroxydopamine-induced nigrostriatal denervation was sufficient to induce significant changes in the gastrointestinal tract. Aside from this toxic approach, the article by O'Donovan and colleagues in this edition of Neurogastroenterology and Motility showed that bilateral nigral injection of adeno-associated virus (AAV)-alpha-synuclein in rats was accompanied by changes in the enteric nervous system and the gut microbiota, which occurred without any apparent brain-to-gut spread of human injected alpha-synuclein. Some changes observed in the gastrointestinal tract of animals injected with AAV-alpha-synuclein were in line with previous observations in Parkinson's disease patients, including increased expression of glial markers, swollen tyrosine hydroxylase-positive varicosities in the submucosal plexus, and decreases in Faecalibacterium and Lachnospiraceae. These findings suggest that, in addition to gut-brain pathways, the brain-to-gut communication may also be involved in Parkinson's disease pathophysiology. In this mini-review, we describe the strengths and limitations of the existing studies on the gut-brain axis in experimental models of parkinsonism and discuss an alternative hypothesis in which the central and enteric nervous system would evolve separately during disease progression.
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http://dx.doi.org/10.1111/nmo.13777DOI Listing
January 2020

The Intestinal Barrier in Parkinson's Disease: Current State of Knowledge.

J Parkinsons Dis 2019 ;9(s2):S323-S329

Inserm, U1235, Nantes, France.

The intestinal barrier, which primarily consists of epithelial cells stitched together with connecting proteins called tight junctions, plays a critical role in health and disease. It is in close contact with the gut microbiota on its luminal side and with the enteric neurons on the tissue side. Both microbiota and the enteric nervous system are regulatory housekeepers of the intestinal barrier. Therefore, the recently observed enteric neuropathology along with gut dysbiosis in Parkinson's disease have prompted research on intestinal permeability in this neurodegenerative disorder. In this mini-review we attempt to concisely summarize the current knowledge on intestinal barrier in Parkinson's disease. We envision future direction research that should be pursued in order to demonstrate its possible role in disease development and progression.
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http://dx.doi.org/10.3233/JPD-191707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839484PMC
July 2020

Examining the Reserve Hypothesis in Parkinson's Disease: A Longitudinal Study.

Mov Disord 2019 11 13;34(11):1663-1671. Epub 2019 Sep 13.

CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805, Villejuif, France.

Background: Whether reserve plays a role in Parkinson's disease (PD) patients has received less attention than in dementia and has been mainly examined in relation with cognitive function.

Objective: To investigate whether reserve plays a role in the severity and progression of motor, cognitive, and nonmotor PD symptoms by examining whether education level (proxy of reserve) is associated with baseline performance and rate of progression.

Methods: We used data from a longitudinal cohort of PD patients (≤5-year disease duration at baseline) annually followed up to 5 years (n = 393; 41% women; mean age = 62.3 years, standard deviation = 10.0; mean disease duration = 2.6 years, standard deviation = 1.5). We examined the relationship of education with time to reach Hoehn and Yahr stage ≥3 using Cox regression and with baseline severity and progression of motor (Movement Disorder Society-Unified Parkinson's Disease Rating Scale parts II and III, gait speed), cognitive (Mini-Mental State Examination), and nonmotor (depression, anxiety, nonmotor symptoms scale, quality of life) symptoms using mixed models.

Results: Education level was not associated with age at onset or diagnosis. Compared with the low-education group, the incidence of Hoehn and Yahr ≥3.0 was 0.42 times lower (95% confidence interval, 0.22-0.82, P = 0.012) in the high-education group. Higher education was associated with better baseline motor function (P < 0.001), but not with the rate of motor decline (P > 0.15). Similar results were observed for cognition. Education was not associated with nonmotor symptoms.

Conclusions: Higher education is associated with better baseline motor/cognitive function in PD, but not with rate of decline, and with a lower risk of reaching Hoehn and Yahr ≥3 during the follow-up. Our observations are consistent with a passive reserve hypothesis for motor/cognitive symptoms. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27854DOI Listing
November 2019

Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification.

Neurobiol Dis 2019 09 9;129:38-43. Epub 2019 May 9.

Institut Fancois Jacob (MIRCen), CEA and Laboratory of Neurodegenerative Diseases, CNRS, 18 Route du Panorama, 92265 Fontenay-Aux-Roses cedex, France. Electronic address:

Lewy bodies and neurites, the pathological signatures found in the central nervous system of Parkinson's disease (PD) patients, are primarily composed of aggregated alpha-synuclein (aSyn). The observation that aSyn aggregates are also found in the enteric nervous system has prompted several studies aimed at developing a diagnostic procedure based on the detection of pathological aSyn in gastrointestinal (GI) biopsies. The existing studies, which have all used immunohistochemistry for the detection of pathological aSyn, have had conflicting results. In the current survey, we analyzed the seeding propensity of aSyn aggregates from GI biopsies. A total of 29 subjects participated to this study, 18 PD patients and 11 controls. For each patient, 2 to 4 GI biopsies were taken from the same site (antrum, sigmoid colon or rectum) and used to seed the aggregation of recombinant aSyn in an assay inspired from the protein misfolding cyclic amplification (PMCA) method. In a subset of patients and controls (14 and 3, respectively), one or two additional biopsies were analyzed by immunohistochemistry for the presence of phosphorylated aSyn histopathology (PASH) using antibodies against phosphorylated aSyn and PGP 9.5. Except for one subject, none of the control samples seeded aSyn aggregation in PMCA reaction. GI biopsies from patients with PD seeded aSyn aggregation in 10 out of 18 cases (7 from the sigmoid colon, 2 from the antrum and one from the rectum). There was good agreement between PMCA and immunohistochemistry results as, except for two cases, all PMCA-positive PD patients were also PASH-positive. Our findings show that the PMCA method we implemented is capable of detecting aSyn aggregates in routine GI biopsies. They also suggest that rectum biopsies do not contain sufficient amounts of aggregated aSyn to detect seeded assembly by PMCA. While encouraging, our findings indicate that further studies are needed to establish the diagnostic potential of the PMCA method we implemented to detect aSyn aggregates in upper GI biopsies.
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http://dx.doi.org/10.1016/j.nbd.2019.05.002DOI Listing
September 2019

Is Parkinson's disease a chronic low-grade inflammatory bowel disease?

J Neurol 2020 Aug 12;267(8):2207-2213. Epub 2019 Apr 12.

Inserm, U1235, 1 rue Gaston Veil, 44035, Nantes, France.

While the pathogenesis of Parkinson's disease is not fully understood, there is increasing evidence that inflammatory responses in the brain are implicated in both disease initiation and progression. The inflammatory process in Parkinson's disease is, however, not limited to the brain but also involves the gastrointestinal tract. High amounts of cytokines and inflammatory markers are found in the colon of Parkinson's disease patients and there is now strong epidemiological and genetical evidence linking Parkinson's disease to inflammatory bowel diseases. Recent findings obtained in both experimental inflammatory bowel diseases and Parkinson's disease further support a bidirectional link between gastrointestinal inflammation and brain neurodegeneration. Altogether, these observations suggest a role for gastrointestinal inflammation in the initiation and progression of Parkinson's disease.
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http://dx.doi.org/10.1007/s00415-019-09321-0DOI Listing
August 2020

French validation of the questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS).

Parkinsonism Relat Disord 2019 06 4;63:117-123. Epub 2019 Mar 4.

Université Clermont Auvergne, NPsy-Sydo, CHRU Clermont-Ferrand, NS-Park/F-CRIN Network, Neurology Department, Clermont-Ferrand, France. Electronic address:

Introduction: The management of impulse control disorders (ICDs) in Parkinson's disease (PD) relies on their early identification, allowing adjustment of antiparkinsonian treatment before these manifestations lead to major social, financial or legal consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) is an English-developed and -validated PD-specific rating scale constructed to support the rating of ICDs and related disorders and the assessment of changes in symptom severity over time, but it has not to date been validated in French.

Methods: We conducted an observational, multicenter, cross-sectional study among a subset of patients (n = 280) from the Drug Interacting with Genes in PD (DIG-PD) cohort, aiming to assess psychometric properties of the French version of QUIP-RS: acceptability, internal consistency, factor analysis, reproductibility and hypotheses testing. In addition to this scale, the following measures were applied: MDS-Unified Parkinson's Disease Rating Scale, Mini-Mental State Examination, Frontal Assessment Behavior, and Ardouin Scale of Behavior in Parkinson's Disease (ASBPD).

Results: Cronbach's alpha coefficient was 0.72 and ranged from 0.25 to 0.55. Regarding test-retest reliability and inter-rater reliability, the Lin concordance coefficient for items was higher than 0.58. The correlations between QUIP-RS and ASBPD were moderate to high except for dopaminergic addiction and hobbyism (r = 0.41 and 0.40 respectively, p < 0.001). No clinically significant correlation was found between QUIP-RS total score (and items) and other scales.

Conclusion: The French version of the QUIP-RS appears to be a valid, reliable, and precise instrument for the assessment of ICDs and related disorders in PD. REGISTRATION NUMBER: clinicaltrials.gov number NCT01564992.
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http://dx.doi.org/10.1016/j.parkreldis.2019.02.026DOI Listing
June 2019

Quality of life predicts outcome of deep brain stimulation in early Parkinson disease.

Neurology 2019 03 8;92(10):e1109-e1120. Epub 2019 Feb 8.

From the Département de Neurologie (W.M.M.S., A.H., T.D.H., F.P., Y.A., M.V.), Hôpital Pitié-Salpêtrière, Centre d'Investigation Clinique 1422, Institut du Cerveau et de la Moelle Epinière, Institut National de Santé et en Recherche Médicale, Assistance Publique Hôpitaux de Paris, France; Institute of Neurology (W.M.M.S.), Konolfingen; Department of Neurology (W.M.M.S.), University Hospital Bern and University of Bern, Switzerland; Medtronic (L.T.), Minneapolis, MN; Institute of Clinical Neuroscience & Medical Psychology and Department of Neurology (A.D., L.W.), Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany; Movement Disorder Unit, Neurology (P.K.), CHU Grenoble Alpes; Grenoble Institut des Neurosciences (P.K., V.F., A. Kistner), University Grenoble Alpes; Inserm U1216 (P.K., V.F., A. Kistner), Grenoble, France; Department of Clinical Neurosciences (Neurology) (P.K.), Faculty of Medicine, University of Geneva, Switzerland; Coordinating Center for clinical trials of the Philipps University of Marburg (J.R., C.S.-B.); Neurochirurgische Klinik im Neurozentrum (A.F., L.P., S.P., J. Volkmann, K.K., G.D.),Christian-Albrechts-Universität Kiel; Neurologische Klinik und Poliklinik (J. Volkmann), Universitätsklinikum Würzburg; Department of Neurology (H.S.D., M.T.B., G.R.F., L.T.), University Hospital Cologne; Research Centre Jülich (G.R.F.); Klinik für Neurologie (T.D.H., A. Kühn, A. Kupsch) and Klinik für Neurochirurgie (G.-H.S.), Campus Virchow, Charité-Universitätsmedizin Berlin; Praxis Kupsch (A. Kupsch), Berlin, Germany; Service de Neurochirurgie (E.S.) and Service de Neurologie (V.F.), Hôpital Michallon, Centre Hospitalo-Universitaire, Grenoble; Departments of Neurosurgery (P.P.C.), Neurology (F.O.-M., C.B.-C.), and Clinical Pharmacology (C.B.-C.), University Hospital of Toulouse; ToNIC (F.O.-M., C.B.-C.), Toulouse Neuroimaging Center, University of Toulouse, Inserm, UPS, France; Department of Neurosurgery (J. Vesper), Universitätsklinikum Düsseldorf, Germany; Departments of Neurosurgery (S.D.) and Neurology (D.M.), Rouen University Hospital and University of Rouen; INSERM U1239 (D.M.), Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan; Service de Neurologie (P. Damier, P. Derkinderen), CHU Nantes, Hôpital Laënnec, France; Paracelsus-Elena-Klinik Kassel (F.S.-D., C.T.); Department of Neurosurgery (C.T.), University Medical Center Göttingen; Division of Functional and Restorative Neurosurgery and Centre for Integrative Neuroscience (A.G.), Tübingen; Abteilung für Neurologie (T.W.), Reha-Zentrum Bad Gögging, Passauer Wolf; Department for Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research (D.W.), University of Tübingen; Division of Stereotactic and Functional Neurosurgery (M.O.P.), University Medical Center Freiburg, Germany; Departments of Functional and Stereotactic Neurosurgery and Radiosurgery (J.-.M.R.) and Neurology (T.W.), Timone University Hospital, INSERM, Marseille; Institut des Sciences Cognitives Marc Jeannerod (S.T.), CNRS, UMR 5229, Université de Lyon; Centre Expert Parkinson (S.T.), Service de Neurologie C, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurosurgery (P.M.), University Hospital of Neurology and Neurosurgery, Hospices Civils de Lyon, Université de Lyon; Department of Neurology (J.-L.H.), INSERM-1402, Centre Hospitalier Universitaire de Poitiers, University of Poitiers, France; and Universitätsklinikum Giessen und Marburg (L.T.), Marburg Campus, Germany.

Objective: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications.

Methods: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI.

Results: PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups ( < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group.

Conclusion: Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS.

Clinicaltrialsgov Identifier: NCT00354133.
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http://dx.doi.org/10.1212/WNL.0000000000007037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442017PMC
March 2019

Acute inflammation down-regulates alpha-synuclein expression in enteric neurons.

J Neurochem 2019 03 24;148(6):746-760. Epub 2019 Jan 24.

Inserm, U1235, Nantes, France.

The protein alpha-synuclein whose expression is strongly implicated in Parkinson's disease (PD) is not only expressed in the CNS but also in the enteric nervous system (ENS). The growing body of evidence suggesting that gastrointestinal inflammation is involved in the development of PD led us to investigate the effects of inflammation on alpha-synuclein expression in primary culture of rat ENS and in mice with dextran sulfate sodium-induced colitis. Using western blot and qPCR, we found that both lipopolysaccharide and a combination of tumor necrosis factor-α and interleukin 1-β decreased the expression levels of alpha-synuclein in primary culture of rat ENS, an effect that was prevented in the presence of the p38 inhibitors SB203580 and BIRB 796. Lipopolysaccharide and tumor necrosis factor-α/interleukin 1-β had no effect on alpha-synuclein expression in primary culture of rat CNS and in human erythroid leukemia cells. In mice, acute but not chronic dextran sulfate sodium-induced colitis was associated with a decreased expression of colonic alpha-synuclein. As a whole, our findings indicate that acute inflammatory insults down-regulate alpha-synuclein expression in the ENS via a p38 pathway. They provide new insights into the widely discussed concepts of alpha-synuclein expression and aggregation in the ENS in PD and raise issues about the possible role of gastrointestinal inflammation in the development of PD. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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http://dx.doi.org/10.1111/jnc.14656DOI Listing
March 2019

The Gut and Parkinson's Disease: Hype or Hope?

J Parkinsons Dis 2018 ;8(s1):S31-S39

Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark.

In the last two decades it has become clear that Parkinson's disease (PD) is associated with a plethora of gastrointestinal symptoms originating from functional and structural changes in the gut and its associated neural structures. This is of particular interest not only because such symptoms have a major impact on the quality of life of PD patients, but also since accumulating evidence suggests that in at least a subgroup of patients, these disturbances precede the motor symptoms and diagnosis of PD by years and may thus give important insights into the origin and pathogenesis of the disease. In this mini-review we attempt to concisely summarize the current knowledge after two decades of research on the gut-brain axis in PD. We focus on alpha-synuclein pathology, biomarkers, and the gut microbiota and envision the development and impact of these research areas for the two decades to come.
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http://dx.doi.org/10.3233/JPD-181477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311363PMC
October 2019

Enteric alpha-synuclein expression is increased in Crohn's disease.

Acta Neuropathol 2019 02 30;137(2):359-361. Epub 2018 Nov 30.

Inserm, U1235, Place Gaston Veil, 44035, Nantes, France.

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http://dx.doi.org/10.1007/s00401-018-1943-7DOI Listing
February 2019

Can the gut be the missing piece in uncovering PD pathogenesis?

Parkinsonism Relat Disord 2019 02 12;59:26-31. Epub 2018 Nov 12.

Inserm, U1235, Faculté de Médecine, 1 rue Gaston Veil, F-44035 Nantes, France; University Nantes, Faculté de Médecine, 1 rue Gaston Veil, F-44035 Nantes, France; CHU Nantes, Clinical Gerontology Department, Bd Jacques Monod, F-44093 Nantes, France; CHU Nantes, Department of Neurology, Nantes, Bd Jacques Monod, F-44093 Nantes, France. Electronic address:

It is now well established that Parkinson's disease (PD) is not only a movement disorder of the CNS but also a gastrointestinal disorder affecting the enteric nervous system (ENS). The gut-brain axis is a bidirectional communication between the brain and the gastrointestinal tract, which comprises besides the CNS and the ENS, the intestinal epithelial barrier, the intestinal microbiota and the enteroendocrine systems. In this review, we present the clinical and pathological evidence suggesting that the gut-brain axis is dysfunctional in PD by discussing the possible role of gut microbiota, inflammation and permeability in the development of the disease.
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http://dx.doi.org/10.1016/j.parkreldis.2018.11.014DOI Listing
February 2019

Colonic neuropathology is not associated with autonomic dysfunction in Parkinson's disease.

Parkinsonism Relat Disord 2019 04 18;61:224-227. Epub 2018 Sep 18.

Inserm, U1235, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; University Nantes, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; Inserm, CIC-04, CHU de Nantes, Bd Jacques Monod, F-44093, Nantes, France; CHU Nantes, Department of Neurology, Nantes, Bd Jacques Monod, F-44093, Nantes, France.

Introduction: Dysautonomia in Parkinson's disease (PD) has been shown to be associated with disease severity and especially with the occurrence of dementia. One proposed explanation for this finding is that phosphorylated alpha-synuclein histopathology (PASH), the characteristic pathological feature of PD is more diffuse in dysautonomia-associated PD than in disease without dysautonomia, not only in the central nervous system but also in peripheral autonomic networks. The aim of this study was therefore to determine if colonic alpha-synuclein histopathology is associated with dysautonomia in PD.

Methods: A total of 43 PD patients participated in this study. For each patient, two biopsies were taken in the sigmoid colon and analyzed by immunohistochemistry with antibodies against phosphorylated alpha-synuclein and PGP 9.5. All patients had a complete neuropsychological and neurological assessment along with a comprehensive evaluation of dysautonomia with questionnaires (SCOPA-Aut, NMS-Quest, Rome III constipation criteria and dry eye symptoms) and functional tests (pupillometry, Saxon and Schirmer's tests, heart rate variability, orthostatic blood pressure measure and sympathetic skin response).

Results: Colonic PASH was observed in 20/43 PD patients. No differences were observed in autonomic symptoms and testing between patients with and without PASH.

Conclusions: Although frequent in PD, autonomic dysfunction is not related to colonic PASH. In addition to the existing literature, our findings further suggest that each dysautonomic symptom in PD might not be associated with a more severe or diffuse PASH not only in the central nervous system but also in the peripheral autonomic nervous systems.
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http://dx.doi.org/10.1016/j.parkreldis.2018.09.021DOI Listing
April 2019

Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4).

J Neuropathol Exp Neurol 2018 09;77(9):793-802

Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.

Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images.
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http://dx.doi.org/10.1093/jnen/nly056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097838PMC
September 2018

Hair-pulling disorder complicated by skin-picking disorder: An unknown side-effect of dopamine replacement therapy?

Psychiatry Clin Neurosci 2018 Oct 23;72(10):801-802. Epub 2018 Aug 23.

INSERM Unit U1246, University of Nantes, University of Tours, Nantes, France.

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http://dx.doi.org/10.1111/pcn.12769DOI Listing
October 2018

Characterisation of tau in the human and rodent enteric nervous system under physiological conditions and in tauopathy.

Acta Neuropathol Commun 2018 07 23;6(1):65. Epub 2018 Jul 23.

Inserm, U1235, 1 rue Gaston Veil, F-44035, Nantes, France.

Tau is normally a highly soluble phosphoprotein found predominantly in neurons. Six different isoforms of tau are expressed in the adult human CNS. Under pathological conditions, phosphorylated tau aggregates are a defining feature of neurodegenerative disorders called tauopathies. Recent findings have suggested a potential role of the gut-brain axis in CNS homeostasis, and therefore we set out to examine the isoform profile and phosphorylation state of tau in the enteric nervous system (ENS) under physiological conditions and in tauopathies. Surgical specimens of human colon from controls, Parkinson's disease (PD) and progressive supranuclear palsy (PSP) patients were analyzed by Western Blot and immunohistochemistry using a panel of anti-tau antibodies. We found that adult human ENS primarily expresses two tau isoforms, localized in the cell bodies and neuronal processes. We did not observe any difference in the enteric tau isoform profile and phosphorylation state between PSP, PD and control subjects. The htau mouse model of tauopathy also expressed two main isoforms of human tau in the ENS, and there were no apparent differences in ENS tau localization or phosphorylation between wild-type and htau mice. Tau in both human and mouse ENS was found to be phosphorylated but poorly susceptible to dephosphorylation with lambda phosphatase. To investigate ENS tau phosphorylation further, primary cultures from rat enteric neurons, which express four isoforms of tau, were pharmacologically manipulated to show that ENS tau phosphorylation state can be regulated, at least in vitro. Our study is the first to characterize tau in the rodent and human ENS. As a whole, our findings provide a basis to unravel the functions of tau in the ENS and to further investigate the possibility of pathological changes in enteric neuropathies and tauopathies.
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http://dx.doi.org/10.1186/s40478-018-0568-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055332PMC
July 2018

Longitudinal analysis of impulse control disorders in Parkinson disease.

Neurology 2018 07 20;91(3):e189-e201. Epub 2018 Jun 20.

From the Assistance Publique Hôpitaux de Paris (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Sorbonne Université (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); INSERM (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Institut du cerveau et de la Moelle, Centre d'Investigation Clinique Neurosciences, NS-PARK/FCRIN Network; CNRS (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.); Departments of Neurology and Genetics (J.-C.C., F.C.-D., L.L., C.B., D.G., S.K., G.M., H.Y., A.B., M.V.), Hôpital Pitié-Salpêtrière, Paris; CESP (F.A., A.E.), Faculte de médecine, Université Paris-Sud; Faculte de médecine (F.A., A.E.), UVSQ, Institut National de la Santé et de la Recherche Médicale, Université Paris-Saclay, Villejuif; University of Toulouse 3 (O.R., C.B.-C., F.O.-M), Centre Hospitalo-Universitaire de Toulouse and INSERM; Centre d'Investigation Clinique CIC1436 (O.R., C.B.-C., F.O.-M), NS-PARK/FCRIN Network, Départements de Neurosciences et de Pharmacologie Clinique, NeuroToul COEN Center, Toulouse; Department of Neurology (F.D., A.-R.M.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Clermont-Ferrand; Department of Neurology (P.D.), NS-PARK/FCRIN Network, Centre Hospitalo-Universitaire de Nantes; Department of Neurology (F.B.), Hôpital Foch, Suresnes; Department of Neurology (J.-P.B.), Fondation Rothschild, Paris; Department of Neurology (F.P.), Centre Hospitalier de Versailles; Université Versailles Saint Quentin en Yvelines et Paris Saclay (F.P.), Versailles; Department of Neurology (V.M.), Centre Hospitalo-Universitaire Saint-Antoine, Paris, France; and Department of Health Care Management (P.-C.L.), College of Health Technology, National Taipei University of Nursing and Health Sciences, Taiwan.

Objective: To investigate the longitudinal dose-effect relationship between dopamine replacement therapy and impulse control disorders (ICDs) in Parkinson disease (PD).

Methods: We used data from a multicenter longitudinal cohort of consecutive patients with PD with ≤5 years' disease duration at baseline followed up annually up to 5 years. ICDs were evaluated during face-to-face semistructured interviews with movement disorder specialists. Generalized estimating equations and Poisson models with robust variance were used to study the association between several time-dependent definitions of dopamine agonist (DA) use, taking dose and duration of treatment into account, and ICDs at each visit. Other antiparkinsonian drugs were also examined.

Results: Among 411 patients (40.6% women, mean age 62.3 years, average follow-up 3.3 years, SD 1.7 years), 356 (86.6%) took a DA at least once since disease onset. In 306 patients without ICDs at baseline, the 5-year cumulative incidence of ICDs was 46.1% (95% confidence interval [CI] 37.4-55.7, DA ever users 51.5% [95% CI 41.8-62.1], DA never users 12.4% [95% CI 4.8-30.0]). ICD prevalence increased from 19.7% at baseline to 32.8% after 5 years. ICDs were associated with ever DA use (prevalence ratio 4.23, 95% CI 1.78-10.09). Lifetime average daily dose and duration of treatment were independently associated with ICDs with significant dose-effect relationships. Similar analyses for levodopa were not in favor of a strong association. ICDs progressively resolved after DA discontinuation.

Conclusion: In this longitudinal study of patients with PD characterized by a high prevalence of DA treatment, the 5-year cumulative incidence of ICDs was ≈46%. ICDs were strongly associated with DA use with a dose-effect relationship; both increasing duration and dose were associated with ICDs. ICDs progressively resolved after DA discontinuation.

Clinicaltrialsgov Identifier: NCT01564992.
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http://dx.doi.org/10.1212/WNL.0000000000005816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059034PMC
July 2018

Crohn's and Parkinson disease: is LRRK2 lurking around the corner?

Nat Rev Gastroenterol Hepatol 2018 06;15(6):330-331

Institut des Maladies de l'Appareil Digestif du CHU de Nantes, Université de Nantes, INSERMU1235, Nantes, France.

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http://dx.doi.org/10.1038/s41575-018-0006-9DOI Listing
June 2018

PCSK9 Concentrations in Cerebrospinal Fluid Are Not Specifically Increased in Alzheimer's Disease.

J Alzheimers Dis 2018 ;62(4):1519-1525

L'institut du thorax, Department of Endocrinology, CHU Nantes, Nantes, France.

The role of PCSK9 in Alzheimer's disease (AD) is controversial. We compared cerebrospinal fluid (CSF) PCSK9 concentrations in 36 AD and 31 non-AD patients. CSF PCSK9 levels did not differ between AD and non-AD groups (2.80 versus 2.62 ng/mL). However, PCSK9 CSF levels were increased in AD and non-AD patients with other neurodegenerative process (non-AD ND, n = 20) compared to patients without neurodegenerative disorders (non-ND, n = 11): 2.80 versus 2.30 (p < 0.005) and 2.83 versus 2.30 ng/mL (p = NS), respectively. CSF PCSK9 were positively correlated with AD biomarkers (Aβ1-42, T-tau, and P-tau). PCSK9 concentrations in CSF are increased in neurodegenerative disorders rather than specifically in AD.
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http://dx.doi.org/10.3233/JAD-170993DOI Listing
May 2019

Heterogeneous pattern of autonomic dysfunction in Parkinson's disease.

J Neurol 2018 Apr 20;265(4):933-941. Epub 2018 Feb 20.

Inserm, U1235, 44035, Nantes, France.

Dysautonomic symptoms are frequent non-motor complaints in patients with Parkinson's disease. Numerous neuropathological studies have shown that Lewy bodies and neurites, the pathological hallmarks of Parkinson's disease, are widely distributed throughout the peripheral autonomic nervous systems and across end organs. However, few investigations integrally explored the symptoms and physiology of dysautonomia in Parkinson's disease. We, therefore, performed a comprehensive evaluation of the autonomic function in a prospective group of 45 patients with idiopathic Parkinson's disease. Autonomic components (pupillomotor, tear, salivary, cardiovascular, digestive, urinary, sexual, sudomotor functions and skin sensitivity) were evaluated using questionnaires and functional tests. Skin biopsy was performed for intraepidermal nerve fibre density quantification. In addition, all patients underwent polysomnography and a complete neuropsychological and neurological assessment. The analysis association of autonomic components showed that dysautonomic signs and symptoms were heterogeneously distributed among patients. Skin denervation as assessed by intraepidermal nerve fibre density quantification was only associated with quantitative thermal sensory testing (OR = 12.0, p = 0.02), constipation (OR = 5.5, p = 0.01) and ocular dryness symptoms (OR = 8.29, p = 0.04). Cognitive alteration was associated with cardiovascular symptoms (OR = 4.33, p = 0.03) and dysfunction (OR = 5.83, p = 0.02) as well as with constipation (OR = 5.38, p = 0.02). Axial motor impairment and rapid eye movement (REM) sleep behaviour disorder were not related to any of the autonomic complaint or dysfunction. Our results show that autonomic functions are affected in a heterogeneous pattern in Parkinson's disease, thereby suggesting that the progression of autonomic dysfunction follows an erratic rather than a stepwise progression.
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http://dx.doi.org/10.1007/s00415-018-8789-8DOI Listing
April 2018