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Abstract Introduction People with Parkinson’s Disease (PD) show abnormal gait patterns compromising their independence and quality of life. Among all gait alterations due to PD, reduced step length, increased cadence, and decreased ground-reaction force during the loading response and push-off phases are the most common. Wearable biofeedback technologies offer the possibility to provide correlated single or multi-modal stimuli associated with specific gait events or gait performance, hence promoting subjects’ awareness of their gait disturbances. Moreover, the portability and applicability in clinical and home settings for gait rehabilitation increase the efficiency in the management of PD. The Wearable Vibrotactile Bidirectional Interface (BI) is a biofeedback device designed to extract gait features in real-time and deliver a customized vibrotactile stimulus at the waist of PD subjects synchronously with specific gait phases. The aims of this study were to measure the effect of the BI on gait parameters usually compromised by the typical bradykinetic gait and to assess its usability and safety in clinical practice. Methods In this case series, seven subjects (age: 70.4 ± 8.1 years; H&Y: 2.7 ± 0.3) used the BI and performed a test on a 10-meter walkway (10mWT) and a two-minute walk test (2MWT) as pre-training (Pre-trn) and post-training (Post-trn) assessments. Gait tests were executed in random order with (Bf) and without (No-Bf) the activation of the biofeedback stimulus. All subjects performed three training sessions of 40 min to familiarize themselves with the BI during walking activities. A descriptive analysis of gait parameters (i.e., gait speed, step length, cadence, walking distance, double-support phase) was carried out. The 2-sided Wilcoxon sign-test was used to assess differences between Bf and No-Bf assessments (p

Individuals with Parkinson’s disease (PD) are characterized by gait and balance disorders limiting their independence and quality of life. Home-based rehabilitation programs, combined with drug therapy, demonstrated to be beneficial in the daily-life activities of PD subjects. Sensorized shoes can extract balance- and gait-related data in home-based scenarios and allow clinicians to monitor subjects’ activities. In this study, we verified the capability of a pair of sensorized shoes (including pressure-sensitive insoles and one inertial measurement unit) in assessing ground-level walking and body weight shift exercises. The shoes can potentially be combined with a sensory biofeedback module that provides vibrotactile cues to individuals. Sensorized shoes have been assessed in terms of the capability of detecting relevant gait events (heel strike, flat foot, toe off), estimating spatiotemporal parameters of gait (stance, swing, and double support duration, stride length), estimating gait variables (vertical ground-reaction force, vGRF; coordinate of the center of pressure along the longitudinal axes of the feet, yCoP; and the dorsiflexion angle of the feet, Pitch angle). The assessment compared the outcomes with those extracted from the gold standard equipment, namely force platforms and a motion capture system. Results of this comparison with 9 PD subjects showed an overall median absolute error lower than 0.03 s in detecting the foot-contact, foot-off, and heel-off gait events while performing ground-level walking and lower than 0.15 s in body weight shift exercises. The computation of spatiotemporal parameters of gait showed median errors of 1.62 % of the stance phase duration and 0.002 m of the step length. Regarding the estimation of vGRF, yCoP, and Pitch angle, the median across-subjects Pearson correlation coefficient was 0.90, 0.94, and 0.91, respectively. These results confirm the suitability of the sensorized shoes for quantifying biomechanical features during body weight shift and gait exercises of PD and pave the way to exploit the biofeedback modules of the bidirectional interface in future studies.

Abstract EXecutive-functions Innovative Tool 360° (EXIT 360°) is an original 360° instrument for an ecologically valid and multicomponent evaluation of executive functioning. This work aimed to test the diagnostic efficacy of EXIT 360° in distinguishing executive functioning between healthy controls (HC) and patients with Parkinson’s Disease (PwPD), a neurodegenerative disease in which executive dysfunction is the best-defined cognitive impairment in the early stage. 36 PwPD and 44 HC underwent a one-session evaluation that involved (1) neuropsychological evaluation of executive functionality using traditional paper-and-pencil tests, (2) EXIT 360° session and (3) usability assessment. Our findings revealed that PwPD made significantly more errors in completing EXIT 360° and took longer to conclude the test. A significant correlation appeared between neuropsychological tests and EXIT 360° scores, supporting a good convergent validity. Classification analysis indicated the potential of the EXIT 360° for distinguishing between PwPD and HC in terms of executive functioning. Moreover, indices from EXIT 360° showed higher diagnostic accuracy in predicting PD group membership compared to traditional neuropsychological tests. Interestingly, EXIT 360° performance was not affected by technological usability issues. Overall, this study offers evidence that EXIT 360° can be considered an ecological tool highly sensitive to detect subtle executive deficits in PwPD since the initial phases of the disease.

Although the 6-Minute Walk Test (6MWT) is among the recommended clinical tools to assess gait impairments in individuals with Parkinson’s disease (PD), its standard clinical outcome consists only of the distance walked in 6 min. Integrating a single Inertial Measurement Unit (IMU) could provide additional quantitative and objective information about gait quality complementing standard clinical outcome. This study aims to evaluate the test–retest reliability, validity and discriminant ability of gait parameters obtained by a single IMU during the 6MWT in subjects with mild PD. Twenty-two people with mild PD and ten healthy persons performed the 6MWT wearing an IMU placed on the lower trunk. Features belonging to rhythm and pace, variability, regularity, jerkiness, intensity, dynamic instability and symmetry domains were computed. Test–retest reliability was evaluated through the Intraclass Correlation Coefficient (ICC), while concurrent validity was determined by Spearman’s coefficient. Mann–Whitney U test and the Area Under the receiver operating characteristic Curve (AUC) were then applied to assess the discriminant ability of reliable and valid parameters. Results showed an overall high reliability (ICC ≥ 0.75) and multiple significant correlations with clinical scales in all domains. Several features exhibited significant alterations compared to healthy controls. Our findings suggested that the 6MWT instrumented with a single IMU can provide reliable and valid information about gait features in individuals with PD. This offers objective details about gait quality and the possibility of being integrated into clinical evaluations to better define walking rehabilitation strategies in a quick and easy way.

The early differential diagnosis of Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), is challenging because of an overlap of clinical features and the lack of reliable biomarkers. Neural-derived extracellular vesicles (NDEVs) isolated from blood provide a window into the brain's biochemistry and may assist in distinguishing between PD and APS. We verified in a case-control study whether oligomeric α-Synuclein and Tau aggregates isolated from NDEVs could allow the differential diagnosis of these conditions.Blood sampling and clinical data, including disease duration, motor severity, global cognition, and levodopa equivalent daily dose (LEDD), were collected from patients with a diagnosis of either PD (n = 70), PSP (n = 21), or CBD (n = 19). NDEVs were isolated from serum by immunocapture using an antibody against the neuronal surface marker L1CAM; oligomeric α-Synuclein and aggregated Tau were measured by ELISA.NDEVs analyses showed that oligomeric α-Synuclein is significantly augmented in PD compared to APS, whereas Tau aggregates are significantly increased in APS compared to PD (p

Complexity analysis of electroencephalogram (EEG) signals has emerged as a valuable tool for characterizing Parkinson’s disease (PD). Fractal dimension (FD) is a widely employed method for measuring the complexity of shapes with many applications in neurodegenerative disorders. Nevertheless, very little is known on the fractal characteristics of EEG in PD measured by FD. In this study we performed a spatio-temporal analysis of EEG in PD using FD in four dimensions (4DFD). We analyzed 42 resting-state EEG recordings comprising two groups: 27 PD patients without dementia and 15 healthy control subjects (HC). From the original resting-state EEG we derived the cortical activations defined by a source reconstruction at each time sample, generating point clouds in three dimensions. Then, a sliding window of one second (the fourth dimension) was used to compute the value of 4DFD by means of the box-counting algorithm. Our results showed a significantly higher value of 4DFD in the PD group (p < 0.001). Moreover, as a diagnostic classifier of PD, 4DFD obtained an area under curve value of 0.97 for a receiver operating characteristic curve analysis. These results suggest that 4DFD could be a promising method for characterizing the specific changes in the brain dynamics associated with PD.

REM sleep behavior disorder (RBD) has a tighter link with synucleinopathies than other neurodegenerative disorders. Parkinson’s Disease (PD) patients with RBD have a more severe motor and cognitive impairment; biomarkers for RBD are currently unavailable. Synaptic accumulation of α-Syn oligomers and their interaction with SNARE proteins is responsible for synaptic dysfunction in PD. We verified whether oligomeric α-Syn and SNARE components in neural-derived extracellular vesicles (NDEVs) in serum could be biomarkers for RBD. Forty-seven PD patients were enrolled, and the RBD Screening Questionnaire (RBDSQ) was compiled. A cut-off score > 6 to define probable RBD (p-RBD) and probable non-RBD (p non-RBD) was used. NDEVs were isolated from serum by immunocapture, and oligomeric α-Syn and SNARE complex components VAMP-2 and STX-1 were measured by ELISA. NDEVs’ STX-1A resulted in being decreased in p-RBD compared to p non-RBD PD patients. A positive correlation between NDEVs’ oligomeric α-Syn and RBDSQ total score was found (p = 0.032). Regression analysis confirmed a significant association between NDEVs’ oligomeric α-Syn concentration and RBD symptoms (p = 0.033) independent from age, disease duration, and motor impairment severity. Our findings suggest that synuclein-mediated neurodegeneration in PD-RBD is more diffuse. NDEVs’ oligomeric α-Syn and SNARE complex components’ serum concentrations could be regarded as reliable biomarkers for the RBD-specific PD endophenotype.

The etiology of Parkinson’s disease (PD) is poorly understood, and is strongly suspected to include both genetic and environmental factors. In this context, it is essential to investigate possible biomarkers for both prognostic and diagnostic purposes. Several studies reported dysregulated microRNA expression in neurodegenerative disorders, including PD. Using ddPCR, we investigated the concentrations of miR-7-1-5p, miR-499-3p, miR-223-3p and miR-223-5p—miRNAs involved in the α-synuclein pathway and in inflammation—in the serum and serum-isolated exosomes of 45 PD patients and 49 age- and sex-matched healthy controls (HC). While miR-499-3p and miR-223-5p showed no differences (1), serum concentration of miR-7-1-5p was significantly increased (p = 0.0007 vs. HC) and (2) miR-223-3p serum (p = 0.0006) and exosome (p = 0.0002) concentrations were significantly increased. ROC curve analysis showed that miR-223-3p and miR-7-1-5p serum concentration discriminates between PD and HC (p = 0.0001, in both cases). Notably, in PD patients, both miR-223-3p serum (p = 0.0008) and exosome (p = 0.006) concentrations correlated with levodopa equivalent daily dosage (LEDD). Finally, serum α-synuclein was increased in PD patients compared to HC (p = 0.025), and in patients correlated with serum miR-7-1-5p in (p = 0.05). Our results suggest that both miR-7-1-5p and miR-223-3p, distinguishing PD from HC, have the potential to be useful and non-invasive biomarkers in Parkinson’s disease.

Despite the wide range of proposed biomarkers for Parkinson’s disease (PD), there are no specific molecules or signals able to early and uniquely identify the pathology onset, progression and stratification. Saliva is a complex biofluid, containing a wide range of biological molecules shared with blood and cerebrospinal fluid. By means of an optimized Raman spectroscopy procedure, the salivary Raman signature of PD can be characterized and used to create a classification model. Raman analysis was applied to collect the global signal from the saliva of 23 PD patients and related pathological and healthy controls. The acquired spectra were computed using machine and deep learning approaches. The Raman database was used to create a classification model able to discriminate each spectrum to the correct belonging group, with accuracy, specificity, and sensitivity of more than 97% for the single spectra attribution. Similarly, each patient was correctly assigned with discriminatory power of more than 90%. Moreover, the extracted data were significantly correlated with clinical data used nowadays for the PD diagnosis and monitoring. The preliminary data reported highlight the potentialities of the proposed methodology that, once validated in larger cohorts and with multi-centered studies, could represent an innovative minimally invasive and accurate procedure to determine the PD onset, progression and to monitor therapies and rehabilitation efficacy.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor (resting tremor, rigidity, bradykinesia, postural instability, and gait disturbances) and nonmotor symptoms (cognitive, neuropsychiatric, and autonomic problems). In recent years, several studies demonstrated that neurorehabilitation therapy is an effective treatment in addition to pharmacological personalized interventions in persons with PD (PwPD). The main aim of this study was to explore the short-term changes in functional, cognitive, and geriatric domains after a multidimensional rehabilitation program in PwPD (as primary condition) in mild–moderate (M-Ms) to severe (Ss) stages. Our second aim was to compare the effects of multidimensional rehabilitation in M-Ms versus Ss of PD. Twenty-four PwPD in M-Ms to Ss [age (mean ± SD) = 76.25 ± 9.42 years; male/female = 10/14; Hoehn and Yahr (median; IQR) = 4.00; 1.75] were included in a retrospective, observational study. Motor, cognitive, functional, and neuropsychiatric aspects were collected in admission (T0) and in discharge (T1). PwPD were involved in a person-tailored (to individual's needs), inpatient, intensive (5–7 days per week), multidisciplinary (combining cognitive, physical, occupational, and speech therapies), comprehensive, and rehabilitative program. According to Movement Disorders Society Unified Parkinson's Disease Rating Scale III cutoff, PwPD were classified in M-Ms or Ss (M-Ms ≤59; Ss >59); 87.50% of our sample reported significant reduction of functional disability at Barthel Index (p < 0.001). A significant improvement in Token test (p = 0.021), semantic fluency (p = 0.036), Rey's Figure-Copy (p < 0.001), and Raven's Colored Progressive Matrices (p = 0.004) was observed. The pain intensity perception (p < 0.001) and the risk of developing pressure ulcers (p < 0.001) as assessed, respectively, by the Numeric Rating Scale and by the Norton Scale were improved. With regard to the second aim, in M-Ms group, we found a positive correlation between the number of neuromotor sessions and the change in functional disability and language comprehension; in the Ss group, on the other hand, despite a higher number of hospitalization days, the total number of completed sessions was positively associated with the change in visuoconstructional abilities. Our findings suggest that an intensive, inpatient, and multidisciplinary rehabilitation program may improve functional abilities, some strategic cognitive functions, and geriatric aspects in PwPD with mild–moderate motor impairment.

To investigate whether different forms of α-synuclein (α-syn) proteins can induce inflammation and activate the NLRP3 inflammasome, we stimulated with monomeric or aggregated α-syn peripheral blood mononuclear cells of Parkinson disease (PD) patients and age- and sex-matched healthy controls (HC). ASC-speck formation, i.e., the intracellular generation of functionally active inflammasome complexes, as well as the production of inflammasome-related [caspase-1, interleukin 1β (IL-18), and IL-1β], and pro–IL-6, or anti–IL-10 inflammatory cytokines were evaluated. Gastrointestinal permeability, suggested to be altered in PD, was also investigated by measuring plasma concentration of lipopolysaccharide (LPS) and I-FABP (fatty acid–binding protein). ASC-speck expression, as well as IL-18 and caspase-1 production and LPS and I-FABP plasma concentration, was comparable in PD and HC, indicating that α-syn does not stimulate the NLRP3 inflammasome and that PD does not associate with alterations of intestinal permeability. Interestingly, though, IL-1β and IL-6 production was increased, whereas that of IL-10 was reduced in α-syn–stimulated cells of PD compared to HC, suggesting that PD-associated neuroinflammation is not the consequence of the activation of the NLRP3 inflammasome but rather of an imbalance between proinflammatory and anti-inflammatory cytokines.

Blood-based biomarkers are needed to be used as easy, reproducible, and non-invasive tools for the diagnosis and prognosis of chronic neurodegenerative disorders including Parkinson's Disease (PD). In PD, aggregated toxic forms of α-Synuclein (α-Syn) accumulate within neurons in the brain and cause neurodegeneration; α-Syn interaction with SNARE proteins also results in synaptic disfunction. We isolated neural derived extravesicles (NDEs) from peripheral blood of 32 PD patients and 40 healthy controls (HC) and measured the concentrations of oligomeric α-Syn and of the presinaptic SNARE complex proteins: STX-1A, VAMP-2 and SNAP-25. Oligomeric α-Syn was significantly augmented whereas STX-1A and VAMP-2 were significantly reduced in NDEs of PD patients compared to HC (p

Out-of-the-lab instrumented gait testing focuses on steady-state gait and usually does not include gait initiation (GI) measures. GI involves Anticipatory Postural Adjustments (APAs), which propel the center of mass (COM) forward and laterally before the first step. These movements are impaired in persons with Parkinson’s disease (PD), contributing to their pathological gait. The use of a simple GI testing system, outside the lab, would allow improving gait rehabilitation of PD patients. Here, we evaluated the metrological quality of using a single inertial measurement unit for APA detection as compared with the use of a gold-standard system, i.e., the force platforms. Twenty-five PD and eight elderly subjects (ELD) were asked to initiate gait in response to auditory stimuli while wearing an IMU on the trunk. Temporal parameters (APA-Onset, Time-to-Toe-Off, Time-to-Heel-Strike, APA-Duration, Swing-Duration) extracted from the accelerometric data and force platforms were significantly correlated (mean(SD), r: 0.99(0.01), slope: 0.97(0.02)) showing a good level of agreement (LOA [s]: 0.04(0.01), CV [%]: 2.9(1.7)). PD showed longer APA-Duration compared to ELD ([s] 0.81(0.17) vs. 0.59(0.09) p < 0.01). APA parameters showed moderate correlation with the MDS-UPDRS Rigidity, Characterizing-FOG questionnaire and FAB-2 planning. The single IMU-based reconstruction algorithm was effective in measuring APAs timings in PD. The current work sets the stage for future developments of tele-rehabilitation and home-based exercises.

Parkinson's disease (PD) is a multisystem neurological condition affecting different neurotransmitter pathways characterized by aberrant functional connectivity (FC) and perfusion alteration. Since the FC, measuring neuronal activity, and cerebral blood flow (CBF) are closely related through the neurovascular coupling (NVC) mechanism, we aim to assess whether FC changes found in PD mirror perfusion ones. A multimodal MRI study was implemented by acquiring resting state functional MRI (rsfMRI) and arterial spin labeling (ASL) datasets on a group of 26 early PD (66.8 ± 8 years, 22 males, median [interquartile range] Hoehn and Yahr = 1.5 [1]) and 18 age- and sex-matched healthy controls (HCs). In addition, a T1-weighted MPRAGE was also acquired in the same scan session. After a standard preprocessing, resting state networks (RSNs) and CBF maps were extracted from rsfMRI and ASL dataset, respectively. Then, by means of a dual regression algorithm performed on RSNs, a cluster of FC differences between groups was obtained and used to mask CBF maps in the subsequent voxel-wise group comparison. Furthermore, a gray matter (GM) volumetric assessment was performed within the FC cluster in order to exclude tissue atrophy as a source of functional changes. Reduced FC for a PD patient with respect to HC group was found within a sensory-motor network (SMN, pFWE = 0.01) and visual networks (VNs, primary pFWE = 0.022 and lateral pFWE = 0.01). The latter was accompanied by a decreased CBF (primary pFWE = 0.037, lateral pFWE = 0.014 VNs), while no GM atrophy was detected instead. The FC alteration found in the SMN of PD might be likely due to a dopaminergic denervation of the striatal pathways causing a functional disconnection. On the other hand, the changes in connectivity depicted in VNs might be related to an altered non-dopaminergic system, since perfusion was also reduced, revealing a compromised NVC. Finally, the absence of GM volume loss might imply that functional changes may potentially anticipate neurodegeneration. In this framework, FC and CBF might be proposed as early functional biomarkers providing meaningful insights in evaluating both disease progression and therapeutic/rehabilitation treatment outcome.

Fronto-parietal regions are involved in cognitive processes that are commonly affected in Parkinson's disease (PD). The aims of this study were to investigate cerebral blood flow (CBF) and gray matter (GM) volume within the regions belonging to the fronto-parietal circuit in people with PD (pwPD) without dementia, and to assess their association with cognitive performance. Twenty-seven pwPD without dementia (mean [SD] age = 67.4 [8.1] years, 20 males, mean [SD] Montreal Cognitive Assessment, MoCA score = 24.2 [2.9], median [IQR] Hoehn and Yahr scale = 1.5 [1–2]) and twenty-six age- and sex-matched healthy controls (HC) were scanned with arterial spin labeling (ASL) and T1-weighted magnetic resonance imaging (MRI) sequences to investigate CBF and GM volume, respectively. The cognitive performance of the enrolled pwPD was assessed with MoCA, Trail Making Test (TMT, part A, B, B-A), phonemic fluency and semantic fluency tests. The scores were adjusted for age and education. After standard preprocessing, CBF differences between pwPD and HC were tested with a voxel-wise approach. Voxel-based morphometry was used to compare pwPD and HC in terms of GM volume. Both voxel-wise comparisons between pwPD and HC were restricted to regions of the fronto-parietal circuit. The following additional voxel-wise analyses were performed within regions showing either perfusion or GM volume alterations: (1) correlation with neuropsychological test scores; (2) subgroup comparison after median split on each neuropsychological test score. Family-wise error-corrected (FWE) p-values lower than 0.05 were considered significant. Significant hypoperfusion was identified in the left inferior parietal lobule (IPL, ppeak = 0.037) and in the bilateral superior parietal lobule (SPL, left hemisphere: ppeak = 0.037; right hemisphere: ppeak = 0.049) of pwPD when compared to HC. No significant GM atrophy was observed. Local hypoperfusion did not correlate with any neuropsychological test scores. However, significantly lower CBF was observed in the left SPL and IPL of the pwPD subgroup who performed poorer on TMT part A in comparison with the pwPD subgroup that performed better. Perfusion alterations may occur in parietal regions of pwPD without dementia, and may be associated with lower visuomotor skills. Parietal CBF may be considered as a suitable early biomarker for longitudinal studies investigating cognitive decline in PD.

Parkinson’s disease (PD) patients using dopamine agonists can develop withdrawal symptoms, referred to as dopamine agonist withdrawal syndrome (DAWS), under dose tapering or discontinuation of these drugs. DAWS includes a severe stereotypical cluster of psychiatric and psychological symptoms encompassing severe mood and anxiety disturbances, autonomic symptoms, as well as generalized pain and drug cravings. However, symptoms of withdrawal of dopamine replacement therapies (DRT) are not simply limited to dopamine agonists tapering, as observed in PD patients on deep brain stimulation after dopaminergic drugs withdrawal related to surgery. To date, no DRT-related withdrawal syndrome has been described in PD patients who discontinue rasagiline, an irreversible inhibitor of monoamine oxidase-B (MAO-B). Here we report three PD patients who developed a severe withdrawal syndrome after rasagiline suspension. The syndrome was mainly characterized by prominent psychiatric disorders (depression, anxiety with panic attacks, dysphoria, and agitation) associated with fatigue, generalized pain, and autonomic manifestations (closely resembling symptoms of DAWS). In our opinion, this report suggests the importance of closely monitoring PD patients undergoing rasagiline suspension for withdrawal symptoms and provides interesting points of reflection on the role of rasagiline and other MAO-B inhibitors in mood disorders.

Executive dysfunction represents a common non-motor symptom in Parkinson’s disease (PD), with a substantial negative impact on daily functioning and quality of life. Assessing executive functions (EFs) with ecological tools is therefore essential. The ecological limitations of traditional neuropsychological tests have led to increased use of virtual reality and 360° environment-based tools for the assessment of EFs in real life. The study aims to evaluate the efficacy and usability of the EXecutive-Functions Innovative Tool 360° (EXIT 360°), a 360°-based tool for the evaluation of EFs in PD. Twenty-five individuals with PD and 25 healthy controls (HC) will be assessed with a conventional neuropsychological battery and EXIT 360° delivered via a head-mounted display. EXIT 360° will show a domestic scenario and seven different subtasks of increasing complexity, and will collect verbal responses, reaction times, and physiological data. We expect that EXIT 360° will be judged usable, engaging, and challenging. Moreover, we expect to find a highly convergent (conventional test and EXIT 360°) and diagnostic validity (individuals with PD vs. HC). The validation of EXIT 360° will allow for the adoption of a fast, ecological, and useful instrument for PD screening, likely transforming the assessment for the clinic and the patient.

The etiology of Parkinson’s disease (PD), a progressive nervous system disorder that affects movement, is still unknown; both genetic and environmental factor are believed to be involved in onset of the disease and its development. Herpes simplex virus type 1 (HSV-1), in particular, is suspected to have a role in PD. Paired Immunoglobulin-like type 2 receptor alpha (PILRA) is an inhibitory receptor that down-regulates inflammation and is expressed on innate immune cells. The PILRA rs1859788 polymorphism is protective against Alzheimer’s disease, even in relation with HSV-1 antibody titers, but no data are available in PD. We analyzed HSV-1 antibody titers and PILRA rs1859788 in PD (n = 51) and age-and sex-matched healthy controls (HC; n = 73). Results showed that HSV-1, but not cytomegalovirus (CMV) or human herpes virus type 6 (HHV-6) antibody titers were significantly higher in PD compared to HC (p = 0.045). The rs1859788 polymorphism was not differentially distributed between PD and HC, but the minor allele A was more frequently carried by PD (68%) compared to HC (50%) (p = 0.06). Notably, the rs1859788 minor allele A was statically more frequent in male PD (65%) compared to male HC (37%) (p = 0.036). Finally, no relation was found between HSV-1 antibody titers and PILRA genotype. Results herein suggest an involvement of HSV-1 in PD and indicate a possible interaction between PILRA gene polymorphisms and this neuropathology.

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