Genetic risk variants in New Yorkers of Puerto Rican and Dominican Republic heritage with Parkinson's disease.

There is a paucity of genetic characterization in people with Parkinson's disease (PD) of Latino and Afro-Caribbean descent. Screening LRRK2 and GBA variants in 32 New Yorkers of Puerto Rican ethnicity with PD and in 119 non-Hispanic-non-Jewish European PD cases revealed that Puerto Rican participants were more likely to harbor the LRRK2-p.G2019S variant (15.6% vs. 4.2%, respectively). Additionally, whole exome sequencing of twelve Puerto Rican and Dominican PD participants was performed as an exploratory study.

Serotonin Syndrome Precipitated by Paxlovid Initiation.

A female in her early 40s taking buspirone, quetiapine, and daily kratom presented to the emergency department two days after starting a course of Paxlovid for a mild COVID-19 infection with diffuse tremors, ocular clonus, diaphoresis, and confusion consistent with serotonin syndrome (SS). The patient was treated with oral lorazepam, and her symptoms significantly improved within one hour without the need for additional dosing. To our knowledge, this is the first reported case of SS in a COVID-19-positive patient who was prescribed Paxlovid. Clinicians should be mindful of the potential interactions of Paxlovid with serotonergic agents, and they should consider reducing the dose of these agents or selecting other therapeutics to treat COVID-19 infection in these patients.

Using eDNA metabarcoding to understand the effect of fire on the diet of small mammals in a woodland ecosystem.

Food acquisition is a fundamental process that drives animal distribution and abundance, influencing how species respond to changing environments. Disturbances such as fire create significant shifts in available dietary resources, yet, for many species, we lack basic information about what they eat, let alone how they respond to a changing resource base. In order to create effective management strategies, faunal conservation in flammable landscapes requires a greater understanding of what animals eat and how this change following a fire. What animals eat in postfire environments has received little attention due to the time-consuming methodologies and low-resolution identification of food taxa. Recently, molecular techniques have been developed to identify food DNA in scats, making it possible to identify animal diets with enhanced resolution. The primary aim of this study was to utilize eDNA metabarcoding to obtain an improved understanding of the diet of three native Australian small mammal species: yellow-footed antechinus (Antechinus flavipes), heath mouse (Pseudomys shortridgei), and bush rat (Rattus fuscipes). Specifically, we sought to understand the difference in the overall diet of the three species and how diet changed over time after fire. Yellow-footed antechinus diets mostly consisted of moths, and plants belonging to myrtles and legume families while bush rats consumed legumes, myrtles, rushes, and beetles. Heath mouse diet was dominated by rushes. All three species shifted their diets over time after fire, with most pronounced shifts in the bush rats and least for heath mice. Identifying critical food resources for native animals will allow conservation managers to consider the effect of fire management actions on these resources and help conserve the species that use them.

Differences in Sex-Specific Frequency of Glucocerebrosidase Variant Carriers and Familial Parkinsonism.

BACKGROUND: Although men and women with the LRRK2 G2019S variant appear to be equally likely to have Parkinson's disease (PD), the sex-distribution among glucocerebrosidase (GBA) variant carriers with PD, including limited to specific variant severities of GBA, is not well understood. Further, the sex-specific genetic contribution to PD without a known genetic variant is controversial. OBJECTIVES: To better understand sex differences in genetic contribution to PD, especially sex-specific frequencies among GBA variant carriers with PD (GBA PD) and LRRK2-G2019S variant carriers with PD (LRRK2 PD). METHODS: We assess differences in the sex-specific frequency in GBA PD, including in subsets of GBA variant severity, LRRK2 PD, and idiopathic PD in an Ashkenazi Jewish cohort with PD. Further, we expand prior work evaluating differences in family history of parkinsonism. RESULTS: Both idiopathic PD (267/420 men, 63.6%) (P < 0.001) and GBA PD overall (64/107, 59.8%) (P = 0.042) were more likely to be men, whereas no difference was seen in LRRK2 PD (50/99, 50.5%) and LRRK2/GBA PD (5/10, 50%). However, among GBA PD probands, severe variant carriers were more likely to be women (15/19 women, 79.0%) (P = 0.005), whereas mild variant carriers (44/70 men, 62.9%) (P = 0.039) and risk-variant carriers (15/17 men, 88.2%) (P = 0.001) were more likely to be men. CONCLUSIONS: Our study demonstrates that the male-sex predominance present in GBA PD overall was not consistent across GBA variant severities, and a female-sex predominance was present among severe GBA variant carriers. Therefore, research and trial designs for PD should consider sex-specific differences, including across GBA variant severities. © 2022 International Parkinson and Movement Disorder Society.

Refractory Seizures Secondary to Vitamin B6 Deficiency in Parkinson Disease: The Role of Carbidopa-Levodopa.

Carbidopa-levodopa has been used for more than 50 years in the treatment of Parkinson disease (PD) and other movement disorders. Pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 (pyridoxine), is involved in the decarboxylation of levodopa to dopamine; carbidopa, which is combined with levodopa to reduce peripheral levodopa conversion and minimize peripheral dopamine side effects, binds irreversibly with PLP. As a result, carbidopa-levodopa may cause vitamin B6 deficiency and associated sequelae, including seizures, especially in high doses. A 78-year-old gentleman with a 6-year history of PD on carbidopa-levodopa therapy and recent weight loss presented with new-onset myoclonus and focal to bilateral tonic-clonic seizures. Workup for vascular, infectious, malignant, metabolic, and autoimmune causes of seizure was unrevealing. The folate level was critically low at <2.20 ng/dL. Video EEG studies showed moderate cerebral dysfunction and seizures with diffuse onsets. Several anti-seizure medications (ASMs) were unsuccessfully tried, so empiric treatment with high-dose steroids was initiated eventually alongside intravenous vitamin B6 therapy. Following introduction of these interventions, the patient had no further epileptic events. The vitamin B6 level came back as undetectable at <1 µg/dL. The patient was discharged to a rehabilitation center for improved strength and function. At the time of writing, he remained on two ASMs as well as IV B6 supplementation. Vitamin B6 is a required cofactor in the decarboxylation of levodopa to dopamine, and high levodopa dosages may cause B6 deficiency; in addition, carbidopa binds B6 irreversibly. We recommend screening of vitamin B6 levels in PD patients, especially those requiring high or increasing doses of carbidopa-levodopa and those with poor nutrition.

Association of Olfactory Performance With Motor Decline and Age at Onset in People With Parkinson Disease and the LRRK2 G2019S Variant.

BACKGROUND AND OBJECTIVES: There is clinical and phenotypic heterogeneity in LRRK2 G2019S Parkinson disease (PD), including loss of smell. Olfactory scores have defined subgroups of LRRK2 PD at baseline. We now extend this work longitudinally to better determine features associated with olfactory classes and to gain further insight into this heterogeneity. METHODS: Evaluation of 162 patients with LRRK2 PD and 198 patients with idiopathic PD (IPD) from the LRRK2 Ashkenazi Jewish Consortium was performed, with follow-up available for 92 patients with LRRK2 PD and 74 patients with IPD. Olfaction (University of Pennsylvania Smell Identification Test [UPSIT]), motor function (Unified Parkinson Disease Rating Scale), and cognition (Montreal Cognitive Assessment), as well as sleep, nonmotor, and mood, were measured. Gaussian mixture models were applied on the UPSIT percentile score to determine subgroups based on olfactory performance. Linear mixed effects models, using PD duration as the time scale, assessed the relationship between UPSIT subgroup membership and motor/cognitive change. RESULTS: Baseline olfaction was better in LRRK2 PD compared with IPD (mean UPSIT ± SD: 24.2 ± 8.8 vs 18.9 ± 7.6), with higher mean percentile scores (difference: 15.3 ± 11.6) (p < 0.001) and less frequent hyposmia (55.6% vs 85.4%; p < 0.001). Analysis suggested 3 classes among LRRK2 PD. Age at onset in LRRK2 PD was earlier in the worst olfaction group (group 1), compared with groups 2 and 3 (54.5 ± 11.1 vs 61.7 ± 9.3) (p = 0.012), and separately in the hyposmic group overall (55.0 ± 11.3 vs 61.7 ± 9.1) (p < 0.001). Longitudinal motor deterioration in LRRK2 PD was also significantly faster in the worst UPSIT group than the best UPSIT group (group 3 vs group 1: B = 0.31, SE = 0.35 vs B = 0.96, SE = 0.28) (rate difference = -0.65, SE = 0.29) (p = 0.03). However, olfactory group membership was not significantly associated with cognitive decline. DISCUSSION: In this large LRRK2 cohort with longitudinal analysis, we extend prior work demonstrating subgroups defined by olfaction in LRRK2 G2019S PD and show that the worst olfaction group has earlier age at PD onset and more rapid motor decline. This supports a subgroup of LRRK2 PD that might show more rapid change in a clinical trial of LRRK2-related agents and highlights the need to integrate careful phenotyping into allocation schema in clinical trials of LRRK2-related agents. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that worse olfactory scores were associated with an earlier age at symptomatic onset and a faster rate of motor deterioration in patients with LRRK2 PD.

Contrasting responses of native and introduced mammal communities to fire mosaics in a modified landscape.

Planned fire is increasingly recognized as an important tool in conservation, but other factors such as land-use change may hinder the ability of land managers to use fire for the benefit of biodiversity. The mosaic of past fires in native vegetation may interact with the mosaic of other land-cover types in human-modified landscapes, yet the effects of these interactions on mammal communities are unknown. We investigated the responses of ground-dwelling mammal community composition and species richness to interactions between land cover and post-fire vegetation growth-stage mosaics in southern Australia. This fire-prone, human-modified landscape features a fine-scale fire mosaic in native vegetation patches surrounded by pasture, horticulture, and peri-urban environments. We measured the composition of land-cover types and fire mosaics (landscape structure) at multiple scales of up to 1257 ha surrounding 129 study sites, and considered native and introduced species together and separately. Land-cover composition was the primary driver of community composition: native species favored areas with a greater proportion of native heathy woodland, whereas introduced species were associated with landscapes comprising more cleared land. The fire mosaic also influenced community composition and species richness: greater growth-stage diversity was associated with native habitat-specialist communities and fewer introduced species. In areas with more cleared land, native species richness increased when there was a greater proportion of mid-successional vegetation, demonstrating that the effect of fire mosaics on mammal diversity depended on land-cover composition. The positive relationship between introduced species richness and cleared land extent was also stronger in recently burned sites than in other growth stages, suggesting that introduced species are well suited to more modified areas of the landscape. Land managers need to consider the underlying land-cover composition and the potential interactions it may have with fire mosaics and species composition. In this landscape a greater diversity of growth stages may disadvantage introduced species yet an increase in mid-successional vegetation in more modified areas would be likely to benefit native mammal communities. Our study highlights that fire management may need to be tailored depending on the context of land use and the species of interest.

An Open-Label Phase 2a Study to Evaluate the Safety and Tolerability of Perampanel in Cervical Dystonia.

BACKGROUND: Cervical dystonia (CD) is the most common focal isolated dystonia. Preclinical studies report that AMPA-selective glutamate receptor antagonists improve dystonia. Perampanel is a clinically available, AMPA receptor antagonist that has shown efficacy and safety in epilepsy. OBJECTIVES: To determine safety and tolerability of perampanel in CD. METHODS: We performed a phase 2a, open-label, multicenter study to evaluate tolerability and safety of perampanel in CD. Included subjects had primary CD; those on botulinum toxin were 8 weeks post last injection. All subjects received perampanel 2 mg/day, titrated 2 mg weekly over 6 weeks, to maximum 12 mg/day; maintenance phase was 4 weeks, ending at week 10. Primary endpoints included tolerability, defined as ability to remain on perampanel for the maintenance period, at any dose level and safety, determined from adverse events (AEs) collected at each visit. Secondary exploratory endpoints included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), quality of life (cervical dystonia impact profile [CIDP]-58) and Clinical Global Impression of change (CGI). RESULTS: CD participants (n = 25) were recruited. Eight subjects withdrew; 4 because of AEs, 3 for other reasons and 1 lost to follow up. One subject tolerated 12 mg/day. Eight subjects (30.8%) tolerated 2 mg, whereas 19.2% tolerated 4 mg/day, and 15.4% tolerated 6 mg or 8 mg/day. All subjects experienced AEs. The most common AEs were dizziness, imbalance, and irritability. Exploratory endpoints of TWSTRS showed some improved pain scores and CIDP-58 improved sleep. CONCLUSIONS: Tolerability to perampanel was variable in CD subjects. Lower doses would be considered for future studies in this population.

Correlation between adolescent orthodontic quality of life and ABO Discrepancy Index in an orthodontic treatment-seeking population: A cross-sectional study.

OBJECTIVE: To evaluate the association between adolescents' orthodontic quality of life before initiating orthodontic treatment and their objective case complexity as measured by the American Board of Orthodontics' Discrepancy Index (DI). DESIGN AND SETTING: A single-centre, cross-sectional survey study. METHODS: The Orthodontic Quality of Life Assessment Survey (OQoLAS) was administered to 240 adolescents (aged 11-14 years) during their record-gathering appointment. After completion of the survey, a DI score was calculated for each patient based on pretreatment measurements. Pearson correlation coefficients, r, were used to assess the association of DI scores with OQoLAS total and subdomain scores. A multiple linear regression of OQoLAS total scores adjusting for age, gender and DI scores was conducted. RESULTS: The study did not find a strong correlation between OQoLAS and DI scores (r = 0.10; P = 0.6497). On average, the OQoLAS scores (functional, emotional and social subdomains of OQoLAS) were slightly higher among girls than among boys but there was no statistical difference for total OQoLAS score between boys and girls (42.4 vs. 45.4, P = 0.2005). However, there was a significant difference in oral health perception rating between boys and girls, with girls being more likely to rate their oral health positively (adjusted P = 0.0226). The total DI scores of boys with respect to girls were not statistically different (P = 0.4256). The components of the DI that showed highest score were for cephalometric measures, followed by overjet; and the lowest scores were for lateral open bite and buccal posterior crossbite. The measure of association analysis did not show any strong correlation between the OQoLAS (total score and subdomain scores), and DI score or any of its components. CONCLUSION: Malocclusion severity was not found to be correlated with orthodontic quality of life in adolescents aged 11-14 years seeking orthodontic treatment.

Cognitive Functioning of Glucocerebrosidase (GBA) Non-manifesting Carriers.

Mutations and variants in the glucocerebrosidase (GBA) gene are among the most common genetic risk factors for the development of Parkinson's disease (PD). Yet, penetrance is markedly reduced, and less is known about the burden of carrying a single mutation among those without diagnosed PD. Motor, cognitive, psychiatric, and olfactory functioning were assessed in 30 heterozygous GBA mutation carriers without PD (the majority of whom had mild GBA mutations) and 49 non-carriers without PD. Study focus was on domains affected in GBA mutation carriers with PD, as well as those previously shown to be abnormal in GBA mutation carriers without PD. GBA mutation carriers showed poorer performance on the Stroop interference measure of executive functioning when controlling for age. There were no group differences in verbal memory, Montreal Cognitive Assessment (MoCA), overall motor score, or presence of REM sleep behavior disorder or depression. Although total olfaction scores did not differ, GBA mutation carriers with hyposmia had lower global cognition scores than those without hyposmia. As anticipated by the low penetrance of GBA mutations, these findings suggest that pre-manifest non-motor or motor features of PD may not present in most GBA mutation carriers. However, there is support that there may be a subtle difference in executive functioning among some non-manifesting heterozygous GBA mutation carriers, and, combined with olfaction, this may warrant additional scrutiny as a potential biomarker for pre-manifest and pre-clinical GBA related PD.

Dysregulation of mitochondrial and proteolysosomal genes in Parkinson's disease myeloid cells.

An increasing number of identified Parkinson's disease (PD) risk loci contain genes highly expressed in innate immune cells, yet their role in pathology is not understood. We hypothesize that PD susceptibility genes modulate disease risk by influencing gene expression within immune cells. To address this, we have generated transcriptomic profiles of monocytes from 230 individuals with sporadic PD and healthy subjects. We observed a dysregulation of mitochondrial and proteasomal pathways. We also generated transcriptomic profiles of primary microglia from brains of 55 subjects and observed discordant transcriptomic signatures of mitochondrial genes in PD monocytes and microglia. We further identified 17 PD susceptibility genes whose expression, relative to each risk allele, is altered in monocytes. These findings reveal widespread transcriptomic alterations in PD monocytes, with some being distinct from microglia, and facilitate efforts to understand the roles of myeloid cells in PD as well as the development of biomarkers.

Survey design for precise fire management conservation targets.

Common goals of ecological fire management are to sustain biodiversity and minimize extinction risk. A novel approach to achieving these goals determines the relative proportions of vegetation growth stages (equivalent to successional stages, which are categorical representations of time since fire) that maximize a biodiversity index. The method combines data describing species abundances in each growth stage with numerical optimization to define an optimal growth-stage structure that provides a conservation-based operational target for managers. However, conservation targets derived from growth-stage optimization are likely to depend critically on choices regarding input data. There is growing interest in the use of growth-stage optimization as a basis for fire management, thus understanding of how input data influence the outputs is crucial. Simulated data sets provide a flexible platform for systematically varying aspects of survey design and species inclusions. We used artificial data with known properties, and a case-study data set from southeastern Australia, to examine the influence of (1) survey design (total number of sites and their distribution among growth stages) and (2) species inclusions (total number of species and their level of specialization) on the precision of conservation targets. Based on our findings, we recommend that survey designs for precise estimates would ideally involve at least 80 sites, and include at least 80 species. Greater numbers of sites and species will yield increasingly reliable results, but fewer might be sufficient in some circumstances. An even distribution of sites among growth stages was less important than the total number of sites, and omission of species is unlikely to have a major influence on results as long as several species specialize on each growth stage. We highlight the importance of examining the responses of individual species to growth stage before feeding survey data into the growth-stage optimization black box, and advocate use of a resampling procedure to determine the precision of results. Collectively, our findings form a reproducible guide to designing ecological surveys that yield precise conservation targets through growth-stage optimization, and ultimately help sustain biodiversity in fire-prone systems.

The Hsp60 protein of helicobacter pylori displays chaperone activity under acidic conditions.

The heat shock protein, Hsp60, is one of the most abundant proteins in Helicobacter pylori. Given its sequence homology to the Escherichia coli Hsp60 or GroEL, Hsp60 from H. pylori would be expected to function as a molecular chaperone in this organism. H. pylori is an organism that grows on the gastric epithelium, where the pH can fluctuate between neutral and 4.5 and the intracellular pH can be as low as 5.0. This study was performed to test the ability of Hsp60 from H. pylori to function as a molecular chaperone under mildly acidic conditions. We report here that Hsp60 could suppress the acid-induced aggregation of alcohol dehydrogenase (ADH) in the 7.0-5.0 pH range. Hsp60 was found to undergo a conformational change within this pH range. It was also found that exposure of hydrophobic surfaces of Hsp60 is significant and that their exposure is increased under acidic conditions. Although, alcohol dehydrogenase does not contain exposed hydrophobic surfaces, we found that their exposure is triggered at low pH. Our results demonstrate that Hsp60 from H. pylori can function as a molecular chaperone under acidic conditions and that the interaction between Hsp60 and other proteins may be mediated by hydrophobic interactions.

A Case of Myoclonus-Dystonia Responding to Low-frequency Pallidal Stimulation.

BACKGROUND: High-frequency pallidal stimulation has been shown to improve various types of dystonia, including myoclonus-dystonia. CASE REPORT: We report a case of epsilon sarcoglycan mutation-negative myoclonus-dystonia with response to low-frequency bilateral pallidal stimulation. DISCUSSION: Low-frequency pallidal stimulation provides an effective means of treating various dystonias, regardless of genetic status, as in our case, as it provides increased programming options with fewer adverse effects.

Neuropsychiatric characteristics of GBA-associated Parkinson disease.

Mutations in GBA1 are a well-established risk factor for Parkinson disease (PD). GBA-associated PD (GBA-PD) may have a higher burden of nonmotor symptoms than idiopathic PD (IPD). We sought to characterize the relationship between GBA-PD and neuropsychiatric symptoms. Subjects were screened for common GBA1 mutations. GBA-PD (n=31) and non-carrier (IPD; n=55) scores were compared on the Unified Parkinson Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Beck Depression Inventory (BDI), and the State-Trait Anxiety Index (STAI). In univariate comparisons, GBA-PD had a greater prevalence of depression (33.3%) versus IPD (13.2%) (p<0.05). In regression models controlling for age, sex, disease duration, motor disability, and MoCA score, GBA-PD had an increased odds of depression (OR 3.66, 95% CI 1.13-11.8) (p=0.03). Post-hoc analysis stratified by sex showed that, among men, GBA-PD had a higher burden of trait anxiety and depression than IPD; this finding was sustained in multivariate models. Among women, GBA-PD did not confer greater psychiatric morbidity than IPD. These results suggest that GBA1 mutations confer greater risk of neuropsychiatric morbidity in PD, and that sex may affect this association.

Opposing Responses of Bird Functional Diversity to Vegetation Structural Diversity in Wet and Dry Forest.

Disturbance regimes are changing worldwide, and the consequences for ecosystem function and resilience are largely unknown. Functional diversity (FD) provides a surrogate measure of ecosystem function by capturing the range, abundance and distribution of trait values in a community. Enhanced understanding of the responses of FD to measures of vegetation structure at landscape scales is needed to guide conservation management. To address this knowledge gap, we used a whole-of-landscape sampling approach to examine relationships between bird FD, vegetation diversity and time since fire. We surveyed birds and measured vegetation at 36 landscape sampling units in dry and wet forest in southeast Australia during 2010 and 2011. Four uncorrelated indices of bird FD (richness, evenness, divergence and dispersion) were derived from six bird traits, and we investigated responses of these indices and species richness to both vertical and horizontal vegetation diversity using linear mixed models. We also considered the extent to which the mean and diversity of time since fire were related to vegetation diversity. Results showed opposing responses of FD to vegetation diversity in dry and wet forest. In dry forest, where fire is frequent, species richness and two FD indices (richness and dispersion) were positively related to vertical vegetation diversity, consistent with theory relating to environmental variation and coexistence. However, in wet forest subject to infrequent fire, the same three response variables were negatively associated with vertical diversity. We suggest that competitive dominance by species results in lower FD as vegetation diversity increases in wet forest. The responses of functional evenness were opposite to those of species richness, functional richness and dispersion in both forest types, highlighting the value of examining multiple FD metrics at management-relevant scales. The mean and diversity of time since fire were uncorrelated with vegetation diversity in wet forest, but positively correlated with vegetation diversity in dry forest. We therefore suggest that protection of older vegetation is important, but controlled application of low-severity fire in dry forest may sustain ecosystem function by enhancing different elements of FD.

Bird functional diversity decreases with time since disturbance: Does patchy prescribed fire enhance ecosystem function?.

Animal species diversity is often associated with time since disturbance, but the effects of disturbances such as fire on functional diversity are unknown. Functional diversity measures the range, abundance, and distribution of trait values in a community, and links changes in species composition with the consequences for ecosystem function. Improved understanding of the relationship between time since fire (TSF) and functional diversity is critical given that the frequency of both prescribed fire and wildfire is expected to increase. To address this knowledge gap, we examined responses of avian functional diversity to TSF and two direct measures of environmental heterogeneity, plant diversity, and structural heterogeneity. We surveyed birds across a 70-year chronosequence spanning four vegetation types in southeast Australia. Six bird functional traits were used to derive four functional diversity indices (richness, evenness, divergence, and dispersion) and the effects of TSF, plant diversity and structural heterogeneity on species richness and the functional diversity indices were examined using mixed models. We used a regression tree method to identify traits associated with species more common in young vegetation. Functional richness and dispersion were negatively associated with TSF in all vegetation types, suggesting that recent prescribed fire generates heterogeneous vegetation and provides greater opportunities for resource partitioning. Species richness was not significantly associated with TSF, and is probably an unreliable surrogate for functional diversity in fire-prone systems. A positive, relationship between functional evenness and structural heterogeneity was comnon to all vegetation types, suggesting that fine-scale (tens of meters) structural variation can enhance ecosystem function. Species more common in young vegetation were primarily linked by their specialist diets, indicating that ecosystem services such as seed dispersal and insect control are enhanced in more recently burnt vegetation. We suggest that patchy prescribed fire sustains functional diversity, and that controlled use of patchy fire to break up large expanses of mature vegetation will enhance ecosystem function.

Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease.

Mutations in the glucocerebrosidase (GBA1) gene, the most common genetic contributor to Parkinson's disease (PD), are associated with an increased risk of PD in heterozygous and homozygous carriers. While glucocerebrosidase enzyme (GCase) activity is consistently low in Gaucher disease, there is a range of leukocyte GCase activity in healthy heterozygous GBA1 mutation carriers. To determine whether GCase activity may be a marker for PD with heterozygous GBA1 mutations (GBA1 mutation PD, GBA PD), GBA PD patients (n=15) were compared to PD patients without heterozygous GBA1 mutations (idiopathic PD; n=8), heterozygous GBA1 carriers without PD (asymptomatic carriers; n=4), and biallelic mutation carriers with PD (Gaucher disease with PD, GD1 PD; n=3) in a pilot study. GCase activity (nmol/mg protein/hour) in GD1 PD (median [interquartile range]; minimum-maximum: 6.4 [5.7]; 5.3-11) was lower than that of GBA PD (16.0 [7.0]; 11-40) (p=0.01), while GCase activity in GBA PD was lower than idiopathic PD (28.5 [15.0]; 16-56) (p=0.01) and asymptomatic carriers (25.5 [2.5]; 23-27) (p=0.04). Therefore, GCase activity appears to be a possible marker of heterozygous GBA1 mutation PD, and larger studies are warranted. Prospective studies are also necessary to determine whether lower GCase activity precedes development of PD.