Family studies have linked several rare genetic variants to hereditary forms of Parkinson's disease (PD). In addition to these monogenic forms, many PD cases are associated with genetic risk factors. Asymptomatic individuals carrying pathogenic variants linked to PD are at risk of developing the disease later in life, thereby providing a unique opportunity for the detection of the earliest pathophysiological and later clinical changes and, importantly, also of protective and compensatory features and mechanisms. However, the rarity of monogenic PD-causing variants is a major challenge of this approach. In this review, we discuss recent advances in the search for biomarkers in the prodromal/earliest phase of genetically linked PD.
Keywords: Biomarker; genetic Parkinson’s disease; neuroimaging marker; prodromal Parkinson’s disease; seeding amplification assay.
While the cause of most cases of Parkinson’s disease (PD) is still unknown, and age is considered the greatest risk factor, a combination of environmental influences and genetics are thought to affect disease risk and progression. The identification of carriers of pathogenic genetic changes, who have not yet developed motor symptoms of PD, offers the chance to closely monitor developing signs of PD. Some of these signs may be suitable biomarkers and could be used to predict early stages of the disease. In this review, we discuss recent advances in the search for biomarkers in the prodromal/earliest phase of genetically linked PD.