PMC:4927924 / 37162-39795
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4927924","sourcedb":"PMC","sourceid":"4927924","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4927924","text":"OUTLOOK\nThere is now converging and compelling evidence for the existence of a latent phase of PD where disease specific molecular events of intracellular α-synuclein misfolding, oligomer and fibril formation are initiated to eventually cause neuronal dysfunction and cell death. For unknown periods of time this process may remain clinically asymptomatic (‘Preclinical PD’) or may cause motor or nonmotor symptoms that are in themselves unspecific and do not meet current diagnostic criteria for PD (‘Prodromal ‘ PD). Recent experimental data strongly suggest that the evolution and clinical progression of PD may be largely driven by cell-to-cell propagation of pathogenic α-synuclein species in the central and also peripheral autonomic nervous system in a prion-like fashion [151, 152]. Therapeutic interventions should therefore ideally target the triggering pathogenic events as early as possible to achieve not only slowing of disease progression but also forestalling of disease onset. This makes early diagnosis a key priority and creates an urgent need for valid PD biomarkers with predictive validity for PD diagnosis. Until now several nonmotor clinical features have been shown to associate with PD risk and the combined occurrence of RBD and hyposmia in otherwise asymptomatic subjects has been shown to associate with the development of clinically defined PD or other Lewy body disorders in a substantial proportion over a relatively short time. While this makes RBD patients a realistic target population for future disease prevention studies of PD, it falls short of defining PD risk at the population level. Combinations of demographic, clinical, genetic and imaging markers have now been tested in large PD samples and also at the population level with promising results regarding diagnostic accuracy as well as definitions of PD risk. Searching for synuclein deposition in nervous tissue that can be obtained with minimal invasive procedures like colonoscopy or skin punch biopsies has so far yielded inconsistent results, but, if further refined, may open up another window into detecting preclinical PD pathology.\nTaken together, current evidence strongly supports a paradigm shift in the diagnosis of PD with a new focus on defining prodromal stages of the disease. In fact, a task force of the International Parkinson and Movement Disorder Society (MDS) has very recently developed research criteria for the definition of prodromal PD by combining various risk and prodromal markers [153] with the ultimate goal of designing clinical trials to test interventions for disease prevention in at-risk individuals.","divisions":[{"label":"Title","span":{"begin":0,"end":7}}],"tracks":[{"project":"TEST0","denotations":[{"id":"26485429-232-239-1671315","span":{"begin":785,"end":788},"obj":"[\"20846907\"]"},{"id":"26485429-219-226-1671316","span":{"begin":2508,"end":2511},"obj":"[\"26474317\"]"}],"attributes":[{"subj":"26485429-232-239-1671315","pred":"source","obj":"TEST0"},{"subj":"26485429-219-226-1671316","pred":"source","obj":"TEST0"}]},{"project":"2_test","denotations":[{"id":"26485429-20846907-64047544","span":{"begin":785,"end":788},"obj":"20846907"},{"id":"26485429-26474317-64047545","span":{"begin":2508,"end":2511},"obj":"26474317"}],"attributes":[{"subj":"26485429-20846907-64047544","pred":"source","obj":"2_test"},{"subj":"26485429-26474317-64047545","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"TEST0","color":"#93deec","default":true},{"id":"2_test","color":"#ece093"}]}]}}