Serum Butyrylcholinesterase Activity: A Biomarker for Parkinson's Disease and Related Dementia.
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ABSTRACT:
SUBMITTER: Dong MX
PROVIDER: S-EPMC5559914 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Biomarkers from multiple modalities have been shown to correlate with cognition in Parkinson's disease (PD) and in Alzheimer's disease (AD). However, the relationships of these markers with each other, and the use of multiple markers in concert to predict an outcome of interest, are areas that are much less explored. Our objectives in this study were (1) to evaluate relationships among 17 biomarkers previously reported to associate with cognition in PD or AD and (2) to test performance of a five-biomarker classifier trained to recognize AD in identifying PD with dementia (PDD). To do this, we evaluated a cross-sectional cohort of PD patients (n = 75) across a spectrum of cognitive abilities. All PD participants had 17 baseline biomarkers from clinical, genetic, biochemical, and imaging modalities measured, and correlations among biomarkers were assessed by Spearman's rho and by hierarchical clustering. We found that internal correlation among all 17 candidate biomarkers was modest, showing a maximum pairwise correlation coefficient of 0.51. However, a five-marker subset panel derived from AD (CSF total tau, CSF phosphorylated tau, CSF amyloid beta 42, APOE genotype, and SPARE-AD imaging score) discriminated cognitively normal PD patients vs. PDD patients with 80% accuracy, when employed in a classifier originally trained to recognize AD. Thus, an AD-derived biomarker signature may identify PDD patients with moderately high accuracy, suggesting mechanisms shared with AD in some PDD patients. Based on five measures readily obtained during life, this AD-derived signature may prove useful in identifying PDD patients most likely to respond to AD-based crossover therapies.
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Project description:Cholinergic neurotransmission regulates the immune response and inhibits cytokine release after stroke. The changes in the level/activity of blood cholinesterase (ChE) in patients with post-stroke dementia (PSD) are less known. This study aimed to examine post-stroke plasma acetylcholinesterase (AChE) and butylcholinesterase (BChE) and determine whether they are biomarkers for PSD. Thirty patients with PSD, 87 post-stroke patients without dementia (PSNoD), and 117 age- and gender-matched healthy controls were recruited. Missense genetic variants AChE rs1799806 and BChE rs1803274 were genotyped. The plasma AChE level did not differ between the PSD and PSNoD groups. However, BChE levels were significantly lower in the PSD than in the PSNoD group (3300.66 ± 515.35 vs 3855.74 ± 677.60 ng/mL, respectively; p = 0.0033). The activities of total ChE, BChE, and AChE were all lower in the PSD group (19,563.33 ± 4366.03, 7650.17 ± 1912.29, 11,913.17 ± 2992.42 mU/mL, respectively) than in the PSNoD group (23,579.08 ± 5251.55, 9077.72 ± 1727.28, and 14,501.36 ± 4197.17 mU/mL, respectively). When further adjusting for age and sex, significance remained in BChE level and activity and in total ChE activity. BChE rs1803274 was associated with reduced BChE activity, while AChE rs1799806 did not influence AChE activity. The level and activity of BChE, but not of AChE, were decreased in PSD patients and may therefore aid in PSD diagnosis.
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Project description:Caffeine has been considered a neuroprotective agent against Parkinson's disease (PD). Recent metabolomic analysis showed that levels of caffeine and its metabolites were decreased in sera from patients with PD compared with those from healthy controls. We focused on theophylline, which is one of the primary caffeine metabolites, as a candidate biomarker of PD because: (1) its serum level can be measured in hospital laboratories by standardized immunoassay kits for therapeutic drug monitoring and (2) because it is less markedly affected by caffeine intake. This was a pilot study to measure the levels of theophylline in sera of 31 patients with PD and 33 age-matched disease controls using an immunoassay kit. We confirmed the previous finding of significantly lower levels of serum theophylline in the PD group compared with control group (PD: 0.07±0.09 μg/mL, control: 0.18±0.24 μg/mL, p<0.05). Using such an approach of applying known medical biomarkers for neurodegenerative diseases may allow us to skip the process from the discovery phase to clinical application, and subsequently shorten the period of time necessary for biomarker development.
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Project description:BackgroundThe objective of this study was to assess neurofilament light chain as a Parkinson's disease biomarker.MethodsWe quantified neurofilament light chain in 2 independent cohorts: (1) longitudinal cerebrospinal fluid samples from the longitudinal de novo Parkinson's disease cohort and (2) a large longitudinal cohort with serum samples from Parkinson's disease, other cognate/neurodegenerative disorders, healthy controls, prodromal conditions, and mutation carriers.ResultsIn the Parkinson's Progression Marker Initiative cohort, mean baseline serum neurofilament light chain was higher in Parkinson's disease patients (13 ± 7.2 pg/mL) than in controls (12 ± 6.7 pg/mL), P = 0.0336. Serum neurofilament light chain increased longitudinally in Parkinson's disease patients versus controls (P < 0.01). Motor scores were positively associated with neurofilament light chain, whereas some cognitive scores showed a negative association.ConclusionsNeurofilament light chain in serum samples is increased in Parkinson's disease patients versus healthy controls, increases over time and with age, and correlates with clinical measures of Parkinson's disease severity. Although the specificity of neurofilament light chain for Parkinson's disease is low, it is the first blood-based biomarker candidate that could support disease stratification of Parkinson's disease versus other cognate/neurodegenerative disorders, track clinical progression, and possibly assess responsiveness to neuroprotective treatments. However, use of neurofilament light chain as a biomarker of response to neuroprotective interventions remains to be assessed. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Project description:Altered mitochondrial function is characteristic in the substantia nigra in Parkinson's disease (PD). Information about mitochondria in other brain regions such as the cerebral cortex is conflicting mainly because most studies have not contemplated the possibility of variable involvement depending on the region, stage of disease progression and clinical symptoms such as the presence or absence of dementia. RT-qPCR of 18 nuclear mRNAs encoding subunits of mitochondrial complexes and 12 mRNAs encoding energy metabolism-related enzymes; western blotting of mitochondrial proteins; and analysis of enzymatic activities of complexes I, II, II, IV and V of the respiratory chain were assessed in frontal cortex area 8 and the angular gyrus of middle-aged individuals (MA), and those with incidental PD (iPD), long-lasting PD with parkinsonism without dementia (PD) and long-lasting PD with dementia (PDD). Up-regulation of several genes was found in frontal cortex area 8 in PD when compared with MA and in the angular gyrus in iPD when compared with MA. Marked down-regulation of genes encoding mitochondrial subunits and energy metabolism-related enzymes occurs in frontal cortex but only of genes coding for energy metabolism-related enzymes in the angular gyrus in PDD. Significant decrease in the protein expression levels of several mitochondrial subunits encoded by these genes occurs in frontal cortex area 8 and angular gyrus in PDD. Moreover, expression of MT-ND1 which is encoded by mitochondrial DNA is also reduced in PDD. Reduced enzymatic activity of complex III in frontal cortex area 8 and angular gyrus is observed in PD, but dramatic reduction in the activity of complexes I, II, II and IV in both regions characterizes PDD. Dementia in the context of PD is linked to region-specific deregulation of genomic genes encoding subunits of mitochondrial complexes and to marked reduction in the activity of mitochondrial complexes I, II, III and IV.
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Project description:Group-based psychosocial therapy, such as group Cognitive Stimulation Therapy, improves cognition and quality of life in people living with dementia. Neuropsychiatric symptoms and restricted mobility are common complications for people with Parkinson's-related dementia (PRD) and may limit access to, and participation in, group activities. This study describes the development of a condition-specific, home-based psychosocial therapy for people with PRD ready to be trialled in a clinical population.By means of a multistage process, a draft therapy manual was developed in an iterative manner through collaboration with medical experts, researchers and Patient and Public Involvement (PPI) representatives. In stage 1, an extensive literature search of psychosocial therapies for dementia with potential relevance for Parkinson's disease (PD) was undertaken to select a candidate therapy for adaptation. In stage 2, qualitative feedback from stakeholders and intelligence regarding existing nonpharmacological therapies for cognitive impairment in PD was combined to produce a prototype therapy manual. In stage 3, the manual was field tested in: 1) a home-setting using a 25-item assessment tool; and 2) at a local PD support group with PPI representatives. Based on the feedback from this phase, final design modifications were implemented and a draft therapy manual produced.The manual was developed in an iterative manner. Interview and focus group transcripts identified three enduring themes: manual form and content, therapy acceptability by people with PRD, and companion guidance and support. Major adaptations included: removal of discrete levels of task complexity, removal of images that were potentially hallucinogenic or lacked clarity, and updating of the content.We have successfully developed a Cognitive Stimulation Therapy-based psychosocial therapy specifically adapted for people with PRD. The therapy is ready to trial in a pilot randomized controlled study.
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Project description:Hyposmia, identified as reduced sensitivity to odor, is a common non-motor symptom of Parkinson's disease (PD) that antedates the typical motor symptoms by several years. It occurs in ∼90% of early-stage cases of PD. In addition to the high prevalence, the occurrence of hyposmia may also predict a higher risk of PD. Investigations into hyposmia and its relationship with PD may help elucidate the underlying pathogenic mechanisms. This review provides an update of olfactory dysfunction in PD and its potential as a biomarker for this devastating disease.
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Project description:BackgroundParkinson's disease (PD) is a condition that affects movement and is usually seen in those over the age of 50. It is caused by the death of dopaminergic neurons, particularly in the substantia nigra. PD has shifted from being perceived as an uncommon condition to a significant neurological illness, mostly due to the increasing number of elderly individuals and the impact of environmental factors. Parkinson's plus syndromes, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and vascular Parkinsonism (VaP), provide difficulties in distinguishing them clinically from PD since they have similar characteristics.MethodologyA thorough examination was performed utilizing the PubMed, Medline, Scopus, and Web of Science databases. The search utilized specific keywords like "Parkinson's disease," "Parkinson's plus syndrome," "Lewy body dementia," "Alzheimer's dementia," "progressive supranuclear palsy," and "multiple system atrophy." The selection criteria were aimed at English-language literature, with a particular focus on examining the connection between PD and associated disorders or dementias.Results and discussionParkinson's plus syndromes, such as PSP, MSA, CBD, and VaP, exhibit unique clinical characteristics, imaging results, and diverse reactions to levodopa. This makes it difficult to distinguish them from PD. LBD is characterized by Lewy bodies containing α-synuclein, which leads to both motor and cognitive deficits. PD and Alzheimer's disease (AD) exhibit a complex interaction, including common pathogenic processes, genetic predispositions, and clinical characteristics of dementia.ConclusionThe interrelatedness of PD, Parkinson's plus syndromes, LBD, and AD highlights the significance of comprehending shared disease-causing processes. Aberrant protein clumping, impaired functioning of mitochondria, increased oxidative stress, and inflammation in the brain are common factors which can be addressed for specific treatments. More research is essential for understanding complicated connections and developing effective therapies for these sophisticated neurological illnesses.
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Project description:Systemic inflammation is an immune response to a nonspecific insult of either infectious or noninfectious origin and remains a challenge in the intensive care units with high mortality rate. Cholinergic neurotransmission plays an important role in the regulation of the immune response during inflammation. We hypothesized that the activity of butyrylcholinesterase (BChE) might serve as a marker to identify and prognose systemic inflammation. By using a point-of-care-testing (POCT) approach we measured BChE activity in patients with severe systemic inflammation and healthy volunteers. We observed a decreased BChE activity in patients with systemic inflammation, as compared to that of healthy individuals. Furthermore, BChE activity showed an inverse correlation with the severity of the disease. Although hepatic function has previously been found essential for BChE production, we show here that the reduced BChE activity associated with systemic inflammation occurs independently of and is thus not caused by any deficit in liver function in these patients. A POCT approach, used to assess butyrylcholinesterase activity, might further improve the therapy of the critically ill patients by minimizing time delays between the clinical assessment and treatment of the inflammatory process. Hence, assessing butyrylcholinesterase activity might help in early detection of inflammation.
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Project description:We evaluated serum gamma-glutamyltransferase (GGT) and the risk of Parkinson's disease (PD). Using data from the National Health Insurance Service (NHIS) database, we constructed a cohort consisting of individuals aged above 40 years who underwent a health check-up in 2009. After excluding individuals with heavy alcohol consumption, hepatobiliary and pancreatic disorders, and a previous history of PD, each quartile group of baseline serum GGT levels was monitored for the development of PD for 7 years. Adjusted hazard ratios (HRs) for PD were estimated by Cox proportional hazard models adjusting for potential confounding variables. We additionally analyzed the possible interaction between GGT and obesity or metabolic syndrome. Among the 6,098,405 individuals who were included, PD developed in 20,895 individuals during the follow-up (0.34%, 9,512 men and 11,383 women). The top quartile of serum GGT (geometric means, 90.44 IU/L in men and 41.86 IU/L in women) was associated with a lower risk in men (adjusted HR?=?0.72 (95% CI: 0.67-0.76)) and a higher risk in women (adjusted HR?=?1.30 (95% CI: 1.23-1.37)) using the lower GGT quartiles as a reference. Obesity and metabolic syndrome increased PD risk in both sexes, and there was only a subadditive interaction between serum GGT and obesity in women.
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