Wake and non-rapid eye movement sleep dysfunction is associated with colonic neuropathology in Parkinson's disease.

Study Objectives: The body-first Parkinson's disease (PD) hypothesis suggests initial gut Lewy body pathology initially propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels, a disease course presumed to likely occur in PD with rapid eye movement sleep behavior disorder (RBD). We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by non-rapid eye movement (NREM) sleep and wakefulness polysomnographic markers.

Methods: In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining.

Wake and non-rapid eye movement sleep dysfunction is associated with colonic neuropathology in Parkinson's disease.

Study Objectives: The body-first Parkinson's disease (PD) hypothesis suggests initial gut Lewy body pathology that propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels. This disease course may also be the most likely in PD with rapid eye movement sleep behavior disorder (RBD).

Objectives: We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by non-rapid eye movement (NREM) sleep and wakefulness polysomnographic markers.

Detection of alpha-synuclein aggregates in gastrointestinal biopsies by protein misfolding cyclic amplification.

Lewy bodies and neurites, the pathological signatures found in the central nervous system of Parkinson's disease (PD) patients, are primarily composed of aggregated alpha-synuclein (aSyn). The observation that aSyn aggregates are also found in the enteric nervous system has prompted several studies aimed at developing a diagnostic procedure based on the detection of pathological aSyn in gastrointestinal (GI) biopsies. The existing studies, which have all used immunohistochemistry for the detection of pathological aSyn, have had conflicting results.

Can the gut be the missing piece in uncovering PD pathogenesis?

It is now well established that Parkinson's disease (PD) is not only a movement disorder of the CNS but also a gastrointestinal disorder affecting the enteric nervous system (ENS). The gut-brain axis is a bidirectional communication between the brain and the gastrointestinal tract, which comprises besides the CNS and the ENS, the intestinal epithelial barrier, the intestinal microbiota and the enteroendocrine systems. In this review, we present the clinical and pathological evidence suggesting that the gut-brain axis is dysfunctional in PD by discussing the possible role of gut microbiota, inflammation and permeability in the development of the disease.

Colonic neuropathology is not associated with autonomic dysfunction in Parkinson's disease.

Introduction: Dysautonomia in Parkinson's disease (PD) has been shown to be associated with disease severity and especially with the occurrence of dementia. One proposed explanation for this finding is that phosphorylated alpha-synuclein histopathology (PASH), the characteristic pathological feature of PD is more diffuse in dysautonomia-associated PD than in disease without dysautonomia, not only in the central nervous system but also in peripheral autonomic networks. The aim of this study was therefore to determine if colonic alpha-synuclein histopathology is associated with dysautonomia in PD.

Heterogeneous pattern of autonomic dysfunction in Parkinson's disease.

Dysautonomic symptoms are frequent non-motor complaints in patients with Parkinson's disease. Numerous neuropathological studies have shown that Lewy bodies and neurites, the pathological hallmarks of Parkinson's disease, are widely distributed throughout the peripheral autonomic nervous systems and across end organs. However, few investigations integrally explored the symptoms and physiology of dysautonomia in Parkinson's disease.

REM sleep behavior disorder is related to enteric neuropathology in Parkinson disease.

Objective: To determine whether REM sleep behavior disorder (RBD) in Parkinson disease (PD) is associated with lesions and dysfunctions of the autonomic nervous system by evaluating enteric phosphorylated α-synuclein histopathology (PASH) and permeability.

Methods: A total of 45 patients with PD were included in this cross-sectional study. RBD was diagnosed on the basis of a standardized clinical interview and confirmed by polysomnography.

Structural alterations of the intestinal epithelial barrier in Parkinson's disease.

Functional and morphological alterations of the intestinal epithelial barrier (IEB) have been consistently reported in digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. There is mounting evidence that Parkinson's disease (PD) is not only a brain disease but also a digestive disorder. Gastrointestinal involvement is a frequent and early event in the course of PD, and it may be critically involved in the early development of the disease.

Enteric glial cells: new players in Parkinson's disease?

Lewy pathology has been described in neurons of the enteric nervous system in nearly all Parkinson's disease (PD) patients at autopsy. The enteric nervous system not only contains a variety of functionally distinct enteric neurons but also harbors a prominent component of glial cells, the so-called enteric glial cells, which, like astrocytes of the central nervous system, contribute to support, protect, and maintain the neural network. A growing body of evidence supports a role for enteric glial cells in the pathophysiology of gastrointestinal disorders such as inflammatory bowel disease and chronic constipation.

Enteric GFAP expression and phosphorylation in Parkinson's disease.

Enteric glial cells (EGCs) are in many respects similar to astrocytes of the central nervous system and express similar proteins including glial fibrillary acidic protein (GFAP). Changes in GFAP expression and/or phosphorylation have been reported during brain damage or central nervous system degeneration. As in Parkinson's disease (PD) the enteric neurons accumulate α-synuclein, and thus are showing PD-specific pathological features, we undertook the present survey to study whether the enteric glia in PD become reactive by assessing the expression and phosphorylation levels of GFAP in colonic biopsies.

Peripheral autonomic nervous system involvement in Gaucher-related parkinsonism.

The pathological process affects the peripheral autonomic nervous system in the vast majority of sporadic PD patients. Recent reports have shown that patients with a familial form of the disease caused by mutation of the gene encoding LRRK2 and alpha-synuclein also display autonomic abnormalities, especially cardiac sympathetic denervation. In the present report, we have studied the involvement of the peripheral autonomic system in a patient with Gaucher disease-associated parkinsonism.

Activity-dependent secretion of alpha-synuclein by enteric neurons.

There is growing evidence supporting a role of extracellular alpha-synuclein in the spreading of Parkinson's disease (PD) pathology. Recent pathological studies have raised the possibility that the enteric nervous system (ENS) is one of the initial sites of alpha-synuclein pathology in PD. We therefore undertook this survey to determine whether alpha-synuclein can be secreted by enteric neurons.