Who is at Risk of Parkinson Disease? Refining the Preclinical Phase of GBA1 and LRRK2 Variant Carriers: a Clinical, Biochemical, and Imaging Approach

AbstractPurpose of ReviewGenetic variants inGBA1 andLRRK2 genes are the commonest genetic risk factor for Parkinson disease (PD); however, the preclinical profile ofGBA1 andLRRK2 variant carriers who will develop PD is unclear. This review aims to highlight the more sensitive markers that can stratify PD risk in non-manifestingGBA1 andLRRK2 variant carriers.Recent FindingsSeveral case –control and a few longitudinal studies evaluated clinical, biochemical, and neuroimaging markers within cohorts of non-manifesting carriers ofGBA1 andLRRK2 variants.SummaryDespite similar levels of penetrance of PD inGBA1 andLRRK2 variant carriers (10 –30%), these individuals have distinct preclinical profiles.GBA1 variant carriers at higher risk of PD can present with prodromal symptoms suggestive of PD (hyposmia), display increased α-synuclein levels in peripheral blood mononuclear cells, and show dopamine transporter abnormalities.LRRK2 variant carriers at higher risk of PD might show subtle motor abnormalities, but no prodromal symptoms, higher exposure to some environmental factors (non-steroid anti-inflammatory drugs), and peripheral inflammatory profile. This information will help clinicians tailor appropriate screening tests and counseling and facilitate researchers in the development of predictive markers, disease-modifying treatments, and selection of healthy individuals who might benefit from preventive interventions.
Source: Current Neurology and Neuroscience Reports - Category: Neuroscience Source Type: research