Disease Progression

Progression of PD symptomatology varies, and different patterns of symptom presentation and progression have suggested the existence of subtypes of disease.  The identification of biomarkers of disease progression is the subject of intense investigation, as the discovery of such markers would greatly facilitate therapeutics development.

Observation of patterns in the progression of PD histopathology has lead to the hypothesis that PD follows a characteristic staging pattern. The classic histological hallmark of PD is the presence of fibrillar aggregates called Lewy bodies in brain and other tissues. While in advanced stages of illness PD pathology can be widespread in the brain, it is concentrated in certain areas of selective vulnerability.

The Braak hypothesis suggests that PD pathology begins with an infectious assault in the enteric nervous system and slowly progresses rostrally toward the brainstem, midbrain and cortical regions and also that histological evidence of PD can be observed in certain neuronal and non-neuronal tissues far in advance of the presentation of cardinal motor symptoms. Given that a similar progression of clinical symptoms can occur, there has been some attention focused on the Braak hypothesis, though it is unclear whether the observed progression may be initiated by a regional pathogen or may instead reflect a pattern of selective neuronal susceptibility to other factors (Braak and Del Tredici, 2008).