J Clin Neurol.  2006 Jun;2(2):83-91. 10.3988/jcn.2006.2.2.83.

Syndromic Approach to Parkinson's Disease: Role of Functional Imaging

• Lee CS
• Chung SJ
• Kim JS

• KMID: 1700740
• DOI: http://doi.org/10.3988/jcn.2006.2.2.83

Abstract

Current evidence from monogenic Parkinson's disease (PD) supports the view that PD is a clinical syndrome, rather than a single disease entity, and that the heterogeneity of PD indeed reflects different pathogenesis. Recent developments in functional imaging have enabled the in vivo assessment of cellular and molecular pathology of PD with respect to temporal and topographical patterns. We propose that this new technology will be useful for linking monogenic and sporadic PD, and thus, for classifying PD based on the pathogenesis. It will be also useful in clinico-genetic studies exploring susceptibility factors and at-risk groups, which are important for neuroprotective treatment when it becomes available.

Keyword

Functional imaging; Positron emission tomography; Parkinson disease; Pathology; Neuroprotective treatment

MeSH Terms

Parkinson Disease*
Pathology
Pathology, Molecular
Population Characteristics
Positron-Emission Tomography

Figure

• 

  Figure 1 In Parkinson's disease (PD), pathological and clinical features are two major phenotypes, largely determined by pathogenic mechanisms. Pathological phenotype includes the molecular type (e.g. α-synuclein, or tauopathy) and topographical distribution. Clinical phenotype includes the time course (e.g. age at onset, the rate of progression) and symptomatology (e.g. parkinsonism, dementia, or autonomic dysfunction). (1) Molecular pathology reflects underlying pathogenic mechanisms.25 (2) Regional selectivity of pathology is derived from selective vulnerability of affected neurons to the pathogenic process.66 (3) Temporal course of PD also reflects underlying pathogenic mechanisms. For example, mutations in parkin, DJ-1 or PINK1 are associated with young-onset PD with slow progression. Park1 shows a gene-dose effect, more aggressive with greater multiplication (see the text). (4) Symptomatology is determined by the location of pathology. For instance, nigral tauopathy produces parkinsonism, indistinguishable from Lewy body PD.10

• 

  Figure 2 Stepped approach to explore the pathogenesis of sporadic PD. The basic tenet underlying this approach is that subgroups of familial and sporadic PD with similar clinical and pathological phenotypes are likely to share pathogenic mechanisms. (1) Define the spectrum of clinical phenotype, findings of pathological imaging, and genotype in familial monogenic PD. (2) Identify a cluster of sporadic PD, whose clinical phenotype and pathological imaging findings are similar to those of a subtype of familial PD. (3) Epidemiological and clinico-genetic studies are conducted in this relatively homogeneous subgroup of sporadic PD to identify genetic susceptibility factors and gene-environmental interactions.

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