User:Pripriva/Parkinson’s Disease and Gut-Brain Axis: Difference between

Parkinson’s Disease (PD), the second most common neurodegenerative disease after Alzheimer’s Disease, affects 1% of people over 60 years of age ^{[2] [1][3]}. In the past three decades, the number of PD cases globally has doubled from 2.5 million in 1990 to 6.1 million in 2016.^[4][5] In the United States, the estimated prevalence of PD by 2030 is estimated will be ~1.24 million.^[4] These numbers are expected to increase as life expectancy and the age of the general population increase as well.^[4][3]

PD is a multifactorial and multisystem disease.^[5] The neuropathological hallmarks of PD include the loss of dopaminergic neurons in the substantia nigra pars compacta region of the brain (shown in Figure 1) and the presence of aggregated alpha-synuclein.^[1] Alpha-synuclein is a protein encoded by the gene, SNCA, found at the synapses of neurons where it inhibits the release of neurotransmitters.^[4][3][6] While it is most abundantly found in the brain, it is also found to a smaller extent in other tissues, such as the gut and heart.^[6] Under pathological conditions in PD, alpha-synuclein undergoes a conformational change that converts it from a soluble protein into an insoluble oligomer and aggregates into protein inclusions called Lewy Bodies.^[4][3][6] Aggregated alpha-synuclein loses its ability to bind at the membrane, disrupts cellular processes and synaptic formation and eventually leads to neuronal degeneration or cell death (Figure 1).^{[1] [4]} Pathological changes are also found peripherally (outside of the central nervous system) and occurring in earlier stages of the disease.^[5] The mechanisms involved in these neuropathological changes are not well understood.^[3]<-- maybe take out

The clinical presentation of PD include both motor and non-motor symptoms summarized in Figure 2.^[4] PD is primarily defined by its motor symptoms, such as rigidity, abnormal gait, tremor, stiffness, bradykinesia, dystonia.^[1][7] Non-motor symptoms include autonomic dysfunction, olfaction dysfunction, cognitive impairment, and urinogenital complications.^[8][7][5] Diagnosis of PD may be delayed and even misdiagnosed in up to 15% of cases as the earlier stages of PD are hard to recognize, especially when motor symptoms, such as tremor, are absent.^[5] Some of the symptoms of earlier stages of PD are non-motor – hyposmia, depression, asymmetric vague shoulder pain, gastrointestinal (GI) dysfunction, and REM sleep behavior disorder (acting out dreams during REM).^[5][9][8][7] GI symptoms and gut dysbiosis can occur up to 20 years prior to the onset of clinical motor symptoms.^[9] Such features can be potential early PD biomarkers used for early detection and early diagnosis of PD.^[10][11]

crosstalk between the gut and the brain provide an avenue for the

strong link between the gut and PD pathology and disease progression.

Gastrointestinal (GI) dysfunction in PD[edit]

The role of the gut in PD was first suggested over 200 years ago by James Parkinson, when he states, “a disordered state of the stomach and bowels may induce a morbid action in a part of the medulla spinalis”.^[8] However, the crosstalk between the gut and the brain has only been more extensively explored in PD in the last two decades.^[8] There is increasing evidence demonstrating the significant impact that GI dysfunction has in the pathogenesis of PD.^[12]

GI Pathology[edit]

Alpha-synuclein is …. and found in the brain, but is also found in the gut….

pathology can also be found in the gut of PD patients.^[13] There are many in vivo studies that have shown alpha-synuclein pathology in biopsies of intestinal tissue from PD patients.^[14] Pathology is also seen in the motor nucleus of vagus (DMV) in the medulla oblongata of the brain and associated vagal nerve – areas that connect to the GI.^[14] Specifically in the GI tract (Figure 3), pathology has a rostral-caudal gradient pattern where there is no pathology in the upper esophagus, but the most affected regions are the lower esophagus (contributing to the swallowing symptoms) and the stomach with sparse pathology in the colon.^[14]

Paper that talks about alpha syn studies in the gut in PD patients. ^[6]

GI Symptoms and Diagnosis[edit]

GI Anatomy as it relates to PD[edit]

include the timing and expand on the symptoms more[edit]

• upper GI symptoms:
• what is upper? dysphasia is a swallowing impairment that results in inadequate mastication (chewing), body mass index below than 20, weight loss and malnutrition.^[14] Drooling is also common as a result of the difficulties with swallowing and not with saliva secretion, which is actually decreased in PD.^[14]
  • oropharyngeal dysphagia: Swallowing involves three…