PMC:4927924 / 1444-3931
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/4927924","sourcedb":"PMC","sourceid":"4927924","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4927924","text":"INTRODUCTION\nCurrently, the diagnosis of Parkinson’s disease (PD) is anchored on clinical criteria, which require the presence of bradykinesia and at least one further motor symptom out of tremor, rigidity or postural instability [1] and pathological studies have shown a strong correlation between the extent of Lewy Body related cell loss in the Substantia Nigra (SN) and the severity of bradykinesia [2]. However, this clinico-pathological concept of PD is challenged by several lines of evidence: Firstly, it has been noted for more than 20 years that nigral cell loss and striatal dopamine depletion progress to an approximate threshold of at least 40% before the first appearance of clinically defining motor signs [2, 3]. Secondly, Braak and colleagues have proposed a staging scheme of PD pathology with initiation of α-synuclein pathology in the caudal brainstem and the olfactory bulb and subsequent spread to the midbrain and eventually the limbic and neocortex [4]. This hypothesis has been extended by multiple studies suggesting early involvement of the peripheral autonomic nervous system in PD [5, 6]. Thirdly, the hypothesis of extra-nigral or even peripheral onset of disease seems to converge with clinical studies showing that PD patients may experience a variety of nonmotor symptoms before the first appearance of classical motor signs [7–9]. Indeed, hyposmia, constipation, depression and idiopathic REM Sleep Behaviour Disorder (RBD) have been shown to go along with a significantly increased risk to develop PD in otherwise healthy subjects in population-based or other cohort studies [10–17]. Taken together, these findings clearly speak to the existence of a stage of PD where affected subjects may be asymptomatic (‘preclinical PD’) or where they may present with a variety of nonmotor symptoms and/or subtle motor signs that do not meet current diagnostic criteria (‘prodromal PD’) [18, 19] (Table 1). Taken by themselves, however, these prodromal features lack specificity and –with the possible exception of RBD –have poor predictive value for PD. The challenge is, therefore, to characterise and validate markers that would enhance specificity and positive predictivity for currently prediagnostic stages of the illness. Here we review the current evidence for potential markers of preclinical or prodromal PD including clinical motor and nonmotor symptoms, neuroimaging measures, genetic susceptibility factors as well as molecular and biopsy biomarkers.","divisions":[{"label":"Title","span":{"begin":0,"end":12}}],"tracks":[{"project":"TEST0","denotations":[{"id":"26485429-218-223-1671188","span":{"begin":231,"end":232},"obj":"[\"2841426\"]"},{"id":"26485429-236-241-1671189","span":{"begin":404,"end":405},"obj":"[\"16606773\"]"},{"id":"26485429-237-242-1671190","span":{"begin":725,"end":726},"obj":"[\"16606773\"]"},{"id":"26485429-136-141-1671191","span":{"begin":1114,"end":1115},"obj":"[\"22508278\"]"},{"id":"26485429-234-239-1671192","span":{"begin":1361,"end":1362},"obj":"[\"25449044\"]"},{"id":"26485429-231-237-1671193","span":{"begin":1614,"end":1616},"obj":"[\"11502913\"]"},{"id":"26485429-235-241-1671194","span":{"begin":1916,"end":1918},"obj":"[\"22252891\"]"}],"attributes":[{"subj":"26485429-218-223-1671188","pred":"source","obj":"TEST0"},{"subj":"26485429-236-241-1671189","pred":"source","obj":"TEST0"},{"subj":"26485429-237-242-1671190","pred":"source","obj":"TEST0"},{"subj":"26485429-136-141-1671191","pred":"source","obj":"TEST0"},{"subj":"26485429-234-239-1671192","pred":"source","obj":"TEST0"},{"subj":"26485429-231-237-1671193","pred":"source","obj":"TEST0"},{"subj":"26485429-235-241-1671194","pred":"source","obj":"TEST0"}]},{"project":"2_test","denotations":[{"id":"26485429-2841426-64047417","span":{"begin":231,"end":232},"obj":"2841426"},{"id":"26485429-16606773-64047418","span":{"begin":404,"end":405},"obj":"16606773"},{"id":"26485429-16606773-64047419","span":{"begin":725,"end":726},"obj":"16606773"},{"id":"26485429-22508278-64047420","span":{"begin":1114,"end":1115},"obj":"22508278"},{"id":"26485429-25449044-64047421","span":{"begin":1361,"end":1362},"obj":"25449044"},{"id":"26485429-11502913-64047422","span":{"begin":1614,"end":1616},"obj":"11502913"},{"id":"26485429-22252891-64047423","span":{"begin":1916,"end":1918},"obj":"22252891"}],"attributes":[{"subj":"26485429-2841426-64047417","pred":"source","obj":"2_test"},{"subj":"26485429-16606773-64047418","pred":"source","obj":"2_test"},{"subj":"26485429-16606773-64047419","pred":"source","obj":"2_test"},{"subj":"26485429-22508278-64047420","pred":"source","obj":"2_test"},{"subj":"26485429-25449044-64047421","pred":"source","obj":"2_test"},{"subj":"26485429-11502913-64047422","pred":"source","obj":"2_test"},{"subj":"26485429-22252891-64047423","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"TEST0","color":"#eb93ec","default":true},{"id":"2_test","color":"#93ecd1"}]}]}}