Differential involvement of nigral subregions in idiopathic parkinson's disease

In this study, the prevalence of abnormality in putative nigrosome 1 and nigrosome 4 (N1 and N4, respectively) was investigated in early versus late‐stage idiopathic Parkinson's disease (IPD) patients. A total of 128 IPD patients (early stage[n = 89]; late stage[n = 39]) and 15 healthy subjects were scanned for high‐resolution (0.5 × 0.5 × 1.0 mm³) multiecho gradient‐recalled echo MRI and dopamine transporter PET imaging. The MRI data were processed for susceptibility map‐weighted imaging (SMWI) to improve a contrast‐to‐noise ratio, and the images were resliced at 0.5 mm to define N1 and N4. When each side of N1 and N4 was assessed separately for the loss of hyperintensity by two independent reviewers, the consensus review results showed that in early‐stage IPD (178 substantia nigras [SNs]), the loss of hyperintensity was observed more often in only the N1 region (65.2%) when compared to in both N1 and N4 regions (34.8%). In late‐stage IPD (78 SNs), on the other hand, the loss in only the N1 region (25.6%) was less prevalent than in both N1 and N4 (74.4%) (P < 0.0001). Additionally, intact SNs (both in N1 and N4) were observed 17 SNs (9.6%) of the early‐stage IPD patients, whereas it was not found in any SNs of the late‐stage IPD patients (P = 0.005). Moreover, involvement of both N1 and N4 on both sides was found in 19.1% of the early‐stage IPD patients, whereas its incidence was higher (61.5%) in the late‐stage IPD patients (P < 0.0001), suggesting that the loss of hyperintensity in IPD progresses from N1 to N4 as the disease advances. Hum Brain Mapp 39:542–553, 2018. © 2017 Wiley Periodicals, Inc.     

Catecholaminergic neurons in the ventrolateral medulla and nucleus of the solitary tract in the human

Catecholaminergic neurons in the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS) are important because of their presumed roles in autonomic regulation, including the tonic and reflex control of arterial pressure, neuroendocrine functions, and the chemosensitivity associated with the ventral medullary surface. However, little is known about the connections of these neurons in the human brain. As a first step in analyzing the functional biochemical anatomy of catecholamine neurons in the human, we used antisera against tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) to localize medullary catecholamine-containing neurons and processes in the VLM and the NTS. Cells staining for TH were located throughout the VLM. Most cells staining for TH and PNMT, which are therefore adrenergic, occurred in an area of the VLM probably corresponding to the rostroventrolateral reticular nucleus. Axons of TH-immunoreactive neurons in the VLM projected (1) dorsally, in a series of parallel transtegmental trajectories, toward the dorsomedial reticular formation, the NTS, and vagal motor nucleus, (2) longitudinally, through the central tegmental field, as fascicles running parallel to the neuraxis, (3) ventrolaterally toward the ventral surface (VS) of the rostral VLM where they appeared to terminate, and (4) medially into the raphe, where they arborized. Similar systems of fibers were labeled for PNMT; the longitudinal bundles of PNMT-labeled axons were limited to the principal tegmental bundle and concentrated dorsally. Fibers containing PNMT were also identified in the medullary raphe, on the medullary ventral surface, and contacting intraparenchymal blood vessels. In the NTS, neurons exhibited immunoreactivity to both TH and PNMT: Four principal subgroups of TH-immunoreactive neurons were seen: a ventral, an intermediate, a medial, and a dorsal group. Perikarya containing PNMT were restricted to the dorsolateral aspect of the NTS. Processes containing TH and PNMT immunoreactivity were identified in the medial and dorsolateral NTS; others appeared to project between the NTS and the VLM and within the solitary tract. The presence of catecholaminergic fibers of the VLM interconnecting with the NTS, raphe, intraparenchymal microvessels, VS, and possibly the spinal cord suggests that the autonomic and chemoreceptor functions attributed to these neurons also may apply to the human.     

Role of the central amygdaloid nucleus in shaping the discharge of gustatory neurons in the rat parabrachial nucleus

The central amygdaloid nucleus (CeA) receives projection from the parabrachial nucleus (PBN) gustatory neurons and descendingly projects to the PBN. To assess if the CeA is involved in modulating the activity of gustatory neurons in the PBN, the effects of electrical stimulation and electrolytic lesion of CeA on PBN gustatory neurons were observed. Of 60 neurons observed, 30 were classified as NaCl-best, 18 as HCl-best, 5 as Quinine HCl (QHCl)-best, and 7 as sucrose-best. During CeA stimulation, the responses to at least one effective stimulus were inhibited in most PBN neurons, with the response magnitudes to HCl and QHCl significantly decreased (P<0.01). In contrast, bilateral lesions of CeA facilitated the responses to HCl and QHCl (P<0.01). According to the best-stimulus category, the effects on the responses to HCl and QHCl were similarly subjected to these modulations either during electrical stimulation or after electrolytic lesions of CeA. Analyses of across-unit patterns indicated that the CeA stimulation increased the chemical selection of PBN taste neurons while the CeA lesions depressed the effect on the chemical selection between NaCl and QHCl. These findings suggest that the CeA may be involved in mediating feeding behavior via modulating the activity of gustatory neurons of PBN.     

电刺激大鼠杏仁中央核对脑桥臂旁核味觉神经元的影响(英文)

利用电生理学方法观察了电刺激杏仁中央核对脑桥臂旁核味觉神经元的影响。结果表明 :电刺激杏仁中央核抑制大部分臂旁核味觉神经元的活动 ,并且提高臂旁核味觉神经元对五种基本味觉刺激反应的特异性。电刺激杏仁中央核对臂旁核的抑制作用以对盐酸和奎宁刺激的反应尤为明显 (P <0 .0 1) ,并且对这两种厌味刺激反应的抑制作用是基本一致的。本研究的结果提示 ,杏仁中央核可能通过抑制脑干味觉神经元对厌味刺激的反应 ,从而参与对摄食行为的调控     

电刺激大鼠杏仁中央核对脑桥臂旁核味觉神经元的影响

利用电生理学方法观察了电刺激杏仁中央核对脑桥臂旁核味觉神经元的影响.结果表明:电刺激杏仁中央核抑制大部分臂旁核味觉神经元的活动,并且提高臂旁核味觉神经元对五种基本味觉刺激反应的特异性.电刺激杏仁中央核对臂旁核的抑制作用以对盐酸和奎宁刺激的反应尤为明显(P＜0.01),并且对这两种厌味刺激反应的抑制作用是基本一致的.本研究的结果提示,杏仁中央核可能通过抑制脑干味觉神经元对厌味刺激的反应,从而参与对摄食行为的调控.     

Medullary dorsal horn neurons providing axons to both the parabrachial nucleus and thalamus

It has often been suggested that the trigemino- and spino-thalamic pathways are highly implicated in sensory-discriminative aspects of pain, whereas the trigemino- and spino-parabrachial pathways are strongly implicated in affective/emotional aspects of pain. On the other hand, the superficial laminae of the spinal dorsal horn, where many nociceptive neurons are distributed, have been reported to contain projection neurons innervating both the parabrachial nucleus (PBN) and thalamus by way of axon collaterals (Hylden et al., 1989). For the medullary dorsal horn (caudal subnucleus of spinal trigeminal nucleus: Vc), however, the existence of such neurons has not been reported. Thus, in the present study, we examined whether the Vc might contain projection neurons sending their axons to both the thalamus and PBN. Dual retrograde labeling with fluorescence dyes was attempted. In each rat, tetramethylrhodamine-dextran amine and Fluoro-gold were stereotaxically injected into the PBN and thalamic regions, respectively. The proportion of the dually labeled Vc cells in the total population of all labeled Vc cells was about 20%. More than 90% of the dually labeled neurons were distributed in lamina I (marginal zone), less than 10% of them were located in lamina II (substantia gelatinosa), and only a few (about 1%) were found in lamina III (magnocellular zone). The results indicate that some Vc neurons in the superficial laminae mediate nociceptive information directly to the PBN and thalamus by way of axon collaterals and that the vast majority of them project to the ipsilateral PBN and contralateral thalamus.     

Mortality of patients with parkinson's disease treated with levodopa

Summary The effect of levodopa on the mortality of patients with Parkinson's disease was investigated in 349 patients treated with levodopa or levodopa combined with a decarboxylase inhibitor during 1969–1975 inclusive. During the study period, 61 patients died. The expected mortality was 32.99 resulting in a ratio of actual to expected deaths of 1.85. The excess mortality was accounted for by patients with a severe disease at entry and especially, by the less favorable effect of levodopa treatment than in the living patients. In comparison with the prelevodopa era, the reduction of mortality and the increase of life expectancy of patients with Parkinson's disease during levodopa treatment possibly reflect the decrease of the early mortality due to Parkinson's disease.

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Zusammenfassung Die Auswirkung der Levodopa-Behandlung auf die Mortalität von Parkinson-Patienten wurde anhand einer Serie von 349 Fällen untersucht, welche in den Jahren 1969–1975 einerseits mit L-Dopa, andererseits mit L-Dopa zusammen mit Decarboxylasehemmern behandelt wurden. Während der Beobachtungsperiode verstarben 61 Patienten. Die erwartete Mortalität hätte 32,99 betragen müssen, was eine Relation von tatsächlicher zu erwarteter Mortalität von 1,85 ergibt. Für die höhere Mortalität waren Fälle verantwortlich mit schweren Krankheitserscheinungen bei Beginn der Therapie und im besondern auch mit einem geringeren Effekt der L-Dopa-Therapie als bei den überlebenden Patienten. Verglichen mit den Beobachtungen vor Einführung der L-Dopa-Therapie beruht wohl die Verminderung der Mortalität und die erhöhte Lebenserwartung von Parkinson-Patienten unter L-Dopa auf der Abnahme der Frühtodesfälle durch die Parkinson'sche Krankheit.

     

Plasticity of nerve afferents to nigrostriatal neurons in parkinson's disease

Clinical symptoms in Parkinson's disease do not appear until almost total depletion of dopamine has occurred in the striatum, suggesting the existence of compensatory mechanisms to offset the loss of nigrostriatal dopaminergic neurons. This compensation has been attributed mainly to an increased turnover of dopamine in the remaining dopaminergic neurons. Besides this biochemical phenomenon intrinsic to dopaminergic neurons, we tested whether morphological changes in the nerve afferents to the dopaminergic neurons could participate in these compensatory mechanisms. The afferents to the dendrites of dopaminergic neurons were analyzed ultrastructurally in the substantia nigra of parkinsonian patients and matched controls, using simultaneous histochemical detection of acetylcholine-like cation and tyrosine hydroxylase. The size of acetycholine-like cation-containing terminals in contact with dopaminergic dendrites increased significantly by 38% in the substania nigra of parkinsonian patients; whereas their number per section of dopaminergic dendrite showed an increase of 60%, although not reaching statistical significance. The number of the terminals devoid of acetylcholine-like cation per section of dopaminergic dendrite decreased significantly by 52% in the substantia nigra of parkinsonian patients. These results suggest (1) a plasticity of excitatory cholinergic neurons targeting nigral dopaminergic neurons and (2) an involution of noncholinergic nerve terminals, mostly originating from inhibitory nigral, pallidal, and striatal GABAergic neurons. The findings provide evidence of a capacity for neuronal plasticity in the elderly human brain, even in the presence of neurodegenerative disorders.     

Down-regulation of trkA mRNA within nucleus basalis neurons in individuals with mild cognitive impairment and Alzheimer's disease

Recent studies indicate that trkA expression is reduced in end-stage Alzheimer's disease (AD). However, understanding the neuropathologic correlates of early cognitive decline, as well as the changes that underlie the transition from nondemented mild cognitive impairment (MCI) to AD, are more critical neurobiological challenges. In these regards, the present study examined the expression of trkA mRNA in individuals diagnosed with MCI and AD from a cohort of people enrolled in a Religious Orders Study. Individuals with MCI and AD displayed significant reductions in trkA mRNA relative to aged-matched controls, indicating that alterations in trkA gene expression occur early in the disease process. The magnitude of change was similar in MCI and AD cases, suggesting that further loss of trkA mRNA is not necessarily associated with the transition of individuals from nondemented MCI to AD. The loss of trkA mRNA was not associated with education, apolipoprotein E allele status, gender, Braak score, global cognitive score or Mini-Mental Status Examination. In contrast, the loss of trkA mRNA in MCI and AD was significantly correlated with function on a variety of episodic memory tests.     

Electrophysiological identification of neurons in the parabrachial nucleus projecting directly to the hypothalamus in the rat

Experiments were done in urethane anesthetized rats to identify single units in the region of the parabrachial nucleus (PBN) projecting directly to ‘cardiovascular’ responsive sites in either the paraventricular nucleus of the hypothalamus (PVH) or the supraoptic commissure and nucleus (SOC-SON) region. Fifty-five single units were antidromically activated in the ipsilateral PBN by electrical stimulation of either the PVH (n = 27) or SOC-SON region (n = 28) with latencies corresponding to conduction velocities of 0.3–5.1 m/s. The axons of PBN units projecting to the PVH conducted at significantly slower velocities (0.5 ± 0.04m/s) than those projecting to the SOC-SON region (1.6 ± 0.25m/s). These data suggest that aacending fibers from the PBN to the PVH are unmyelinated, whereas those to the SOC-SON region are primarily a little myelinated. In addition, since the PBN is known to receive cardiovascular and visceral afferent inputs, it is suggested that these neurons likely function in relaying this afferent information to hypothalamic areas involved in autonomic regulation.     

帕金森病自主神经功能障碍的回顾性分析

目的探讨帕金森病患者自主神经功能障碍的发生与起病年龄、性别、病程、症状的严重程度等的相关性。方法回顾性分析了2001年1月至2007年1月中国人民解放军总医院神经内科住院的101例帕金森病人,计量资料进行F检验,计数资料进行χ2检验,分析自主神经功能障碍的发生与改良Hoehn-Yahr分级、病程、性别、起病年龄、首发症状与其相关性。结果自主神经功能障碍发生率达74.26%(75/101)。其中便秘的发生率最高,达45.54%。改良Hoehn-Yahr分级1～1.5级30.7%(31/101),2～2.5级33.7%(34/101),3级及以上35.6%(36/101),经χ2检验自主神经功能障碍的发生率与不同级别的H-Y分级有统计学意义(χ2=30.554,P=0.00)。χ2检验结果表明病程长短与自主神经功能障碍有显著性差异(χ2=13.142,P=0.041)。自主神经功能障碍的发生与性别、起病年龄、首发症状无显著性差异。结论帕金森病患者自主神经异常发生率很高,与疾病严重程度及病程有相关性。     

Effects of GABA on neurons of the gustatory and visceral zones of the parabrachial nucleus in rats

Response characteristics of neurons in the gustatory and visceral zone of the parabrachial nucleus (PBN) to γ-aminobutyric acid (GABA) were examined using whole cell recordings in brain slices of the rat. Based on the recording site, neurons were divided into three groups: neurons in the dorsolateral quadrant of the PBN (DL-neurons), neurons in the dorsomedial quadrant of the PBN (DM-neurons) and neurons in the ventromedial quadrant of the PBN (VM-neurons). Recordings were made from 44 DL-, 43 DM-, 39 VM-neurons. Superfusion of GABA resulted in a concentration-dependent reduction in input resistance in 67.5% of the neurons in the PBN (73.1% of the DL-, 62.5% of the DM-, 66.7% of the VM-neurons). No obvious difference of the concentration–response curve was found among three groups. The mean reversal potential of the GABA effect was about −74 mV and no significant differences were observed among three groups of neurons. The GABA response was partly or completely blocked by the GABA_A antagonist bicuculline in all neurons tested. Superfusion of the GABA_A agonist muscimol resulted in a decrease of the input resistance in all neurons tested. It was concluded that GABA functions as an inhibitory neurotransmitter in both gustatory and visceral part of the PBN, mediated in part, by GABA_A receptors.     

Olanzapine in the treatment of hallucinosis in idiopathic parkinson's disease: a cautionary note

BACKGROUND—Hallucinosis is adopaminergic dose limiting complication of the treatment of idiopathicParkinson's disease. Typical neuroleptic medications cannot be usedfor suppressing hallucinosis because the extrapyramidal side effectsworsen parkinsonian motor control. Olanzapine is a novel atypicalantipsychotic drug with few reported extrapyramidal side effects whichmay be more suitable for controlling hallucinosis in these patients.
METHODS—Olanzapine was given to five patients withidiopathic Parkinson's disease and the dosage was titrated until aclinically meaningful reduction in hallucinosis was achieved. Thecommercially available 5 mg, 7.5 mg and 10 mg tablets were used.
RESULTS—After an initial 9 days oftreatment, hallucinosis frequency was significantly reduced, aneffect which was maintained with continued treatment. However,during this early phase of treatment, parkinsonian motor disabilityincreased, which resulted in two of the patients discontinuing medication.
CONCLUSIONS—Olanzapine is effective in thesuppression of hallucinosis in patients with idiopathic Parkinson'sdisease but the currently available dose increments may result in anunacceptable exacerbation of motor disability.

     

Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer's disease

Recent studies indicate that there is a marked reduction in trkA-containing nucleus basalis neurons in end-stage Alzheimer's disease (AD). We used unbiased stereological counting procedures to determine whether these changes extend to individuals with mild cognitive impairment (MCI) without dementia from a cohort of people enrolled in the Religious Orders Study. Thirty people (average age 84.7 years) came to autopsy. All individuals were cognitively tested within 12 months of death (average MMSE 24.2). Clinically, 9 had no cognitive impairment (NCI), 12 were categorized with MCI, and 9 had probable AD The average number of trkA-immunoreactive neurons in persons with NCI was 196, 632 +/- 12,093 (n = 9), for those with MCI it was 106,110 +/- 14,565, and for those with AD it was 86,978 +/- 12,141. Multiple comparisons showed that both those with MCI and those with AD had significant loss in the number of trkA-containing neurons compared to those with NCI (46% decrease for MCI, 56% for AD). An analysis of variance revealed that the total number of neurons containing trkA immunoreactivity was related to diagnostic classification (P < 0.001), with a significant reduction in AD and MCI compared to NCI but without a significant difference between MCI and AD. Cell density was similarly related to diagnostic classification (P < 0.001). There was a significant correlation with the Boston Naming Test and with a global score measure of cognitive function. The number of trkA-immunoreactive neurons was not correlated with MMSE, age at death, education, apolipoprotein E allele status, gender, or Braak score. These data indicate that alterations in the number of nucleus basalis neurons containing trkA immunoreactivity occurs early and are not accelerated from the transition from MCI to mild AD.     

Localization of mu-opioid receptors on amygdaloid projection neurons in the parabrachial nucleus of the rat.

The parabrachial nucleus (PB) is a major relay of noxious and non-noxious visceral sensory information from the nucleus of the solitary tract, spinal cord, and spinal trigeminal nucleus to the forebrain. The nucleus of the solitary tract, spinal cord, and trigeminal dorsal horns contain many enkephalin- and dynorphin-immunoreactive neurons that project to the PB. To study the role of mu-opioid receptors in relaying these inputs, we examined the distribution of mu-opioid receptor immunoreactivity in the PB. The most intense staining was in the external lateral parabrachial subnucleus (PBel), including dendrites extending from the PBel into the lateral crescent subnucleus. Because the Pbel is a major source of projections to the amygdala, we combined retrograde tracing from the central nucleus of the amygdala with immunohistochemistry for mu-opioid receptors. These experiments showed that mu-opioid receptors are expressed by Pbel neurons that project to the amygdala, including those Pbel neurons whose dendrites extend into the lateral crescent subnucleus. These results indicate that mu-opioid receptors in the PB may mediate or modulate nociceptive information relayed to the amygdala from medullary or spinal cord neurons that terminate not only in the Pbel, but also in the adjacent lateral crescent parabrachial subnucleus.     

Influence of nucleus tractus solitarius stimulation and baroreceptor activation on rat parabrachial neurons.

The parabrachial nucleus (PBN) within the dorsolateral pons is a major recipient of autonomic-related inputs from more caudal levels of the brainstem and, in particular, the nucleus of the solitary tract (NTS). Although the anatomical projections from the NTS to the PBN are well characterized, less is known concerning the influence of activating NTS efferents on PBN neurons and the response of the latter to cardiovascular-related inputs. The present study examined the response of PBN neurons to electrical stimulation of the depressor area within the NTS in urethane anesthetized rats, and subsequently, the influence of arterial baroreceptor activation and systemic angiotensin II (ANG II) on these cells. Extracellular single-unit PBN recordings indicated that 92 of 227 (40.5%) cells were orthodromically excited and 35 of 227 (15.4%) inhibited consequent to NTS stimulation. Ten (4.5%) PBN cells displayed antidromic activation from the NTS. Of 41 of 119 neurons responding to both NTS stimulation and baroreceptor activation, 29.3% revealed a excitatory and 31.7% an inhibitory response to the two stimuli. Fifteen PBN cells responded to NTS stimulation, baroreceptor activation, and the administration of systemic ANG II, with six cells displaying either an excitatory or inhibitory response to all three stimuli. These observations provide electrophysiological support for reciprocal connections between the NTS and PBN and indicate the presence of both excitatory and inhibitory projections to the pontine nucleus. A population of neurons influenced by activation of NTS efferents also reveal a similarity of responses to inputs originating from peripheral arterial baroreceptors and systemic ANG II.     

Sexuality in women with parkinson's disease

There is a renewed interest in sexuality in chronic disease states. Whereas there is some literature on male sexuality in Parkinson's disease (PD), no study has been devoted exclusively to women. We compared 27 women who had PD with community controls matched for age and marital status by using the Brief Index of Sexual Functioning in Women. Approximately 50% of both samples were sexually active. The women with PD were more likely to be dissatisfied with the quality of the sexual experiences. There were significant differences in the two groups with respect to anxiety or inhibition, vaginal tightness, and involuntary urination. Preoccupation with health problems interfering with sex and dissatisfaction with body appearance were also more prevalent in parkinsonian women, but not statistically different from controls. The PD patients were less satisfied with their sexual relationships and with their partners, and were more depressed as a group when compared with controls (Beck Depression Inventory of 11.8 vs 6.3). In both groups, age was associated with significant changes in satisfaction and activity. In summary, qualitative differences exist in the sexual experiences of women with PD compared with controls.     

A subpopulation of neurons in the rat rostral nucleus of the solitary tract that project to the parabrachial nucleus express glutamate-like immunoreactivity

In rodents, gustatory information is transmitted from second order neurons in the rostral nucleus of the solitary tract (rNST) to the parabrachial nucleus (PBN) in the pons. The chemical nature of this projection is unknown. Therefore, the goal of the current study was to determine if rNST neurons that project to the PBN express glutamate-like immunoreactivity. Projection neurons were retrogradely labeled following stereotaxic injection of rhodamine-filled latex microspheres into the right PBN of seven rats while glutamate-immunoreactive (GLU-IR) structures were visualized in the same tissue using an immunoperoxidase procedure. The number of single- and double-labeled neurons located in the right (ipsilateral) and left rNST, in each of the nuclear subdivisions as well as their position along the rostral-caudal axis of the rNST was determined. GLU-IR cell bodies were located throughout the rNST. Although the rostral central subdivision contained the highest percentage (33.8%) of GLU-IR perikarya, immunolabeled neurons were most concentrated (number/area of subdivision) within the medial subnucleus. The rostral third of the rNST contained the fewest (20. 5%) and lowest density of GLU-IR cell bodies. The highest percentage of rNST neurons retrogradely labeled from the PBN were located ipsilateral (85.4%) to the pontine injection site, in the middle third of the nucleus (44.2%) and within the rostral central subdivision (52.4%). Overall, 18% of the labeled rNST projection neurons were GLU-IR. The distribution of double-labeled neurons mirrored that of the projection neurons with the largest number located in the ipsilateral rNST (84.5%), middle third of the nucleus (40.5%) and rostral central subdivision (64.7%). These results indicate that glutamate may be a main component of the ascending pathway from the rNST to the PBN. In addition, since GLU-IR neurons were located throughout the rNST and most were not retrogradely-labeled, the current results suggest that glutamate may be an important neurotrans-mitter within the medulla.     

Blood lysosphingolipids accumulation in patients with parkinson's disease with glucocerebrosidase 1 mutations

Introduction: Glucocerebrosidase 1 mutations, the most common genetic contributor to Parkinson's disease (PD), have been associated with decreased glucocerebrosidase enzymatic activity in PD patients with glucocerebrosidase 1 mutations (glucocerebrosidase 1–PD). However, it is unknown whether this decrease in enzymatic activity leads to lysosphingolipid accumulations. Methods: The levels of hexosylsphingosines, globotriaosylsphingosine, sphingomyelin, and sphingomyelin‐509 were measured in dried blood spots from glucocerebrosidase 1–PD patients (n = 23), sporadic PD patients (n = 105), Gaucher disease patients (n = 32), and controls (n = 88) by liquid chromatography‐tandem mass spectrometry. Results: Glucocerebrosidase 1–PD patients had increased hexosylsphingosine levels when compared with sporadic PD patients (P < .001) and controls (P < .0001). Hexosylsphingosine levels were increased in glucocerebrosidase 1 mutation carriers of glucocerebrosidase 1 (L444P; N370S; n = 11, P = .001) and glucocerebrosidase 1 polymorphic variants (E326K, T369M) associated with PD (n = 12, P = .04) when compared with controls. Conclusions: Lysosphingolipid accumulations in PD patients who bear glucocerebrosidase 1 mutations suggest that substrate reduction therapy might be viewed as a possible strategy for glucocerebrosidase 1–PD treatment. © 2018 International Parkinson and Movement Disorder Society