Extensive research has been done using the models of nematode (C. elegans), and fruit fly (Drosophila), mice, and non-human primates.Nine inherited neurodegenerative diseases are caused by the expansion of the CAG trinucleotide and polyQ tract, including Huntingtons disease and the spinocerebellar ataxias. Epigenetics
The presence of epigenetic modifications for certain genes has been demonstrated in this type of pathology. An example is FKBP5 gene, which progressively increases its expression with age and has been related to Braak staging and increased tau pathology both in vitro and in mouse models of AD. Protein misfolding
Several neurodegenerative diseases are classified as proteopathies as they are associated with the aggregation of misfolded proteins. Protein toxicity is one of the key mechanisms of many neurodegenrative diseases. alpha-synuclein: can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinsons disease, dementia with Lewy bodies, and multiple system atrophy. Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as the non-Abeta component (NAC), is found in amyloid plaques in Alzheimers disease. tau: hyperphosphorylated tau protein is the main component of neurofibrillary tangles in Alzheimers disease; tau fibrils are the main component of Pick bodies found in behavioral variant frontotemporal dementia. amyloid beta: the major component of amyloid plaques in Alzheimers disease. prion: main component of prion diseases and transmissible spongiform encephalopathy. Intracellular mechanisms
Protein degradation pathways
Parkinsons disease and Huntingtons disease are both late-onset and associated with the accumulation of intracellular toxic proteins.
Although barium is superior in demonstrating small perforations, the spillage of barium sulfate into the mediastinal and pleural cavities can cause an inflammatory response and subsequent fibrosis and is therefore not used as the primary diagnostic study. If, however, the water-soluble study is negative, a barium study should be performed for better definition.Endoscopy has no role in the diagnosis of spontaneous esophageal perforation. Both the endoscope and insufflation of air can extend the perforation and introduce air into the mediastinum.Patients may also have a pleural effusion high in amylase (from saliva), low pH, and may contain particles of food. Differential diagnosis
Common misdiagnoses include myocardial infarction, pancreatitis, lung abscess, pericarditis, and spontaneous pneumothorax. If esophageal perforation is suspected, even in the absence of physical findings, chest xray, water soluble contrast radiographic studies of the esophagus and a CT scan should be promptly obtained. In most cases, non-operative management is administered based on radiological evidence contained in mediastinal collection. Treatment
With the exception of a few case reports describing survival without surgery, the mortality of untreated Boerhaave syndrome is  100%. Its treatment includes immediate antibiotic therapy to prevent mediastinitis and sepsis, surgical repair of the perforation, and if there is significant fluid loss it should be replaced with IV fluid therapy since oral rehydration is not possible. Even with early surgical intervention (within 24 hours) the risk of death is 25%. References
Further reading
Radiology  Esophageal rupture
Arens, Ann; Ben-Youssef, Leila; Hayashi, Sandra; Smollin, Craig (2016). "Esophageal Rupture After Ghost Pepper Ingestion". The Journal of Emergency Medicine. 51 (6): e141–e143.