Menozzi, E;
Schapira, AHV;
Blandini, F;
Avenali, M;
(2023)
Who is at Risk of Parkinson Disease? Refining the Preclinical Phase of GBA1 and LRRK2 Variant Carriers: a Clinical, Biochemical, and Imaging Approach.
Current Neurology and Neuroscience Reports
10.1007/s11910-023-01259-1.
(In press).
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Abstract
Purpose of Review: Genetic variants in GBA1 and LRRK2 genes are the commonest genetic risk factor for Parkinson disease (PD); however, the preclinical profile of GBA1 and LRRK2 variant carriers who will develop PD is unclear. This review aims to highlight the more sensitive markers that can stratify PD risk in non-manifesting GBA1 and LRRK2 variant carriers. Recent Findings: Several case–control and a few longitudinal studies evaluated clinical, biochemical, and neuroimaging markers within cohorts of non-manifesting carriers of GBA1 and LRRK2 variants. Summary: Despite similar levels of penetrance of PD in GBA1 and LRRK2 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.
| Type: | Article |
|---|---|
| Title: | Who is at Risk of Parkinson Disease? Refining the Preclinical Phase of GBA1 and LRRK2 Variant Carriers: a Clinical, Biochemical, and Imaging Approach |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s11910-023-01259-1 |
| Publisher version: | http://dx.doi.org/10.1007/s11910-023-01259-1 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Parkinson disease · GBA1 · Glucocerebrosidase · LRRK2 · Carrier · Prodromal |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10166547 |
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