Despite considerable progress in understanding the clinical and pathological features of Parkinson's disease (PD), the etiology of this condition is unknown (1,2). Current working hypotheses are based primarily on two plausible explanations: the environmental hypothesis and the genetic hypothesis. The environmental hypothesis, which was widely propagated in the 1980s, appears to have had only limited influence (3). The genetic hypothesis, which gained popularity in the 1990s, stemmed from considerable progress in the development of new molecular genetic techniques and from the description of several large families with a parkinsonian phenotype closely resembling that of sporadic PD (4-6). However, genetic factors still do not explain the etiology of all cases of PD (7). Thus, a combination of environmental and inherited risk factors may play a crucial role in the development of disease in most cases of parkinsonism.
Understanding the causes of PD is further complicated by a lack of in vivo biological markers for diagnosis, which requires reliance on clinical or pathological criteria (8). In addition, rather than being a uniform clinical and pathological entity, PD most likely represents a cluster of heterogeneous syndromes (9,10). In this chapter, we discuss the contributions of epidemiologic, twin, kindred, and association studies in support of the genetic hypothesis of PD.
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