Decreased intestinal acetylcholinesterase in early Parkinson disease

Fedorova, Tatyana D.; Seidelin, Louise B.; Knudsen, Karen A.; Schacht, Anna Christina; Geday, Jacob; Pavese, Nicola; Brooks, David J.; Borghammer, Per

doi:10.1212/wnl.0000000000003633

Cited by 78 publications

(83 citation statements)

References 28 publications

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“…Constipation is very common in the prodromal phase of PD and objective colonic dysfunction has been recently ascertained in PD patients [32]. At a molecular level, the presence of synuclein aggregates in colonic biopsies of PD subjects has been widely discussed as a main diagnostic factor for PD prior to the onset of clinical motor features, although providing controversial results [5, 33], and other differential factors, such as decreased intestinal acetylcholinesterase activity, have been reported in early PD [34]. Although growing attention has been focused on the search for predictive prognostic biomarkers of the disease in the enteric nervous system, no gold standard consensus has been achieved, and mitochondrial and oxidative markers in colonic samples from iRBD and PD patients have not yet been explored.…”

Section: Discussionmentioning

confidence: 99%

Colonic Oxidative and Mitochondrial Function in Parkinson’s Disease and Idiopathic REM Sleep Behavior Disorder

Morén

González‐Casacuberta

Navarro‐Otano

et al. 2017

Parkinson's Disease

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Objective To determine potential mitochondrial and oxidative alterations in colon biopsies from idiopathic REM sleep behavior disorder (iRBD) and Parkinson's disease (PD) subjects. Methods Colonic biopsies from 7 iRBD subjects, 9 subjects with clinically diagnosed PD, and 9 healthy controls were homogenized in 5% w/v mannitol. Citrate synthase (CS) and complex I (CI) were analyzed spectrophotometrically. Oxidative damage was assessed either by lipid peroxidation, through malondialdehyde and hydroxyalkenal content by spectrophotometry, or through antioxidant enzyme levels of superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (Gpx1), and catalase (CAT) by western blot. The presence of mitochondrial DNA (mtDNA) deletions was assessed by long PCR and electrophoresis. Results Nonsignificant trends to CI decrease in both iRBD (45.69 ± 18.15; 23% decrease) and PD patients (37.57 ± 12.41; 37% decrease) were found compared to controls (59.51 ± 12.52, p: NS). Lipid peroxidation was maintained among groups (iRBD: 27.46 ± 3.04, PD: 37.2 ± 3.92, and controls: 31.71 ± 3.94; p: NS). Antioxidant enzymes SOD2 (iRBD: 2.30 ± 0.92, PD: 1.48 ± 0.39, and controls: 1.09 ± 0.318) and Gpx1 (iRBD 0.29 ± 0.12, PD: 0.56 ± 0.33, and controls: 0.38 ± 0.16) did not show significant differences between groups. CAT was only detected in 2 controls and 1 iRBD subject. One iRBD patient presented a single mtDNA deletion.

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Section: Discussionmentioning

confidence: 99%

Colonic Oxidative and Mitochondrial Function in Parkinson’s Disease and Idiopathic REM Sleep Behavior Disorder

Morén

González‐Casacuberta

Navarro‐Otano

et al. 2017

Parkinson's Disease

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“…Pavese and colleagues used 11 C‐donepezil PET, a marker of acetylcholinesterase density in the brain and peripheral organs, to assess parasympathetic innervation in the GIT of patients with early PD. They found that, compared to controls, PD patients had significantly reduced 11 C‐donepezil uptake in the small intestine, colon, and kidneys, providing further support that parasympathetic denervation in these organs is present early in the natural history of PD …”

Section: Molecular Imaging Of Pdmentioning

confidence: 94%

Imaging Markers of Progression in Parkinson's Disease

Strafella

Bohnen

Pavese

et al. 2018

Movement Disord Clin Pract

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Background Parkinson's disease (PD) is the second‐most common neurodegenerative disorder after Alzheimer's disease; however, to date, there is no approved treatment that stops or slows down disease progression. Over the past decades, neuroimaging studies, including molecular imaging and MRI are trying to provide insights into the mechanisms underlying PD. Methods This work utilized a literature review. Results It is now becoming clear that these imaging modalities can provide biomarkers that can objectively detect brain changes related to PD and monitor these changes as the disease progresses, and these biomarkers are required to establish a breakthrough in neuroprotective or disease‐modifying therapeutics. Conclusions Here, we provide a review of recent observations deriving from PET, single‐positron emission tomography, and MRI studies exploring PD and other parkinsonian disorders.

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“…Exclusion criteria were significant medical co‐morbidity including heart, kidney, and liver diseases, current thoracic and abdominal cancers, previous major surgery to the GI tract (except esophagus resection), neurological or psychiatric diseases, substance abuse, decreased kidney function (eGFR <45 mL/min/1.73 m 2 ), significant cardiovascular disease, and cholinergic medications. Sixteen healthy matched subjects from a previously published dataset were used as controls . Seventeen PD patients from the same dataset are used for comparison of colonic parasympathetic denervation.…”

Section: Methodsmentioning

confidence: 99%

“…PMOD version 3.6 software (PMOD Technologies) was used to define volumes of interest (VOI) as previously described …”

Section: Methodsmentioning

confidence: 99%

“…In hollow organs, tissue volume was specified by subtracting volume of luminal fluid and gas using segmentation at thresholds between 0 and 300 HU. The SUV values in the small intestine and colon were corrected for potential differences in organ volumes using regression analyses, in effect removing potential bias imposed by differing volumes between the groups . Since manual outlining of particularly the intestines is time‐consuming, we attempted to simplify the process by analyzing a smaller part of the intestines only.…”

Section: Methodsmentioning

confidence: 99%

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In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients

Fedorova

Knudsen

Hartmann

et al. 2019

Neurogastroenterology Motil

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Background Parasympathetic neuropathy is a key feature in many common disorders, including diabetes, neurological disorders, and cancers, but few objective methods exist for assessing damage to the parasympathetic nervous system, particularly in the gastrointestinal system. This study aimed to validate the use of 11C‐donepezil positron emission tomography (PET) to assess parasympathetic integrity in a group of vagotomized patients. Methods Sixteen healthy controls and 12 patients, vagotomized due to esophagectomy, underwent 11C‐donepezil PET, measurement of colonic transit time, quantification of plasma pancreatic polypeptide (PP), and assessment of subjective long‐term symptoms. Key Results Vagotomized patients had significantly decreased PET signal in the small intestine and colon compared with healthy controls (5.7 [4.4‐7.9] vs 7.4 [4.5‐11.3], P = .01 and 1.4 [1.1‐2.1] vs 1.6 [1.4‐2.4], P < .01, respectively). Vagotomized patients also displayed a significantly increased colonic transit time (2.9 ± 0.9 h vs 1.9 ± 0.8 h), P < .01 and increased volumes of the small intestine and colon (715 ccm [544‐1177] vs 443 ccm [307‐613], P < .01 and 971 ccm [713‐1389] vs 711 ccm [486‐1394], P = .01, respectively). Patients and controls did not differ in PP ratio levels after sham feeding, but PP ratio at 10 minutes. after sham feeding and PET signal intensity in the small intestine was positively correlated (P = .03). Conclusions and Inferences We found significantly decreased 11C‐donepezil signal in the intestine of vagotomized patients, supporting that 11C‐donepezil PET is a valid measure of intestinal parasympathetic denervation.

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Decreased intestinal acetylcholinesterase in early Parkinson disease

Abstract: We found significantly decreased C-donepezil signal in the intestine and kidneys of patients with early PD, suggesting that parasympathetic denervation is present early in the disease course.

Cited by 78 publications

References 28 publications

Colonic Oxidative and Mitochondrial Function in Parkinson’s Disease and Idiopathic REM Sleep Behavior Disorder

Colonic Oxidative and Mitochondrial Function in Parkinson’s Disease and Idiopathic REM Sleep Behavior Disorder

Imaging Markers of Progression in Parkinson's Disease

In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients

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