14 Genetics

Despite considerable progress in the understanding of clinical and pathological features of Parkinson’s disease (PD), the etiology of this condition remains unknown (1,2). There are two major plausible explanations on which current working hypotheses are based. The ‘‘environmental hypothesis,’’ widely propagated in the 1980s, appears to have had only limited influence (3). The scope of environmental factors on causation of PD is discussed in Chapter 15. The ‘‘genetic hypothesis,’’ which was popular in the 1990s, stemmed from significant progress in the development of new molecular genetic techniques and from the description of several large families with a phenotype closely resembling that of sporadic PD (4,5). However, genetic factors still do not explain the etiology of all cases of PD (6). It is reasonable to assume that a combination of environmental and inherited risk factors plays the crucial role in developing disease in most cases of parkinsonism. The era of exploration of these intermingling influences and factors is just beginning. Understanding the etiology of PD is further complicated by a lack of in vivo biological markers for a diagnosis of PD, requiring reliance on