Who is at Risk of Parkinson Disease? Refining the Preclinical Phase of GBA1 and LRRK2 Variant Carriers: a Clinical, Biochemical, and Imaging Approach.
Who is at Risk of Parkinson Disease? Refining the Preclinical Phase of GBA1 and LRRK2 Variant Carriers: a Clinical, Biochemical, and Imaging Approach.
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DOI：
10.1007/s11910-023-01259-1
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发表时间：
2023-04
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
GBA 1和LRRK 2基因的遗传变异是帕金森病（PD）最常见的遗传风险因素;然而，GBA 1和LRRK 2变异携带者将发展PD的临床前特征尚不清楚。本综述旨在强调更敏感的标志物，可以分层PD风险在非表现GBA 1和LRRK 2变异载体。几项病例对照和一些纵向研究评估了GBA 1和LRRK 2变异体非表现携带者队列中的临床、生化和神经影像学标志物。尽管GBA 1和LRRK 2变异携带者的PD突变率水平相似（10-30%），但这些个体具有不同的临床前特征。具有较高PD风险的GBA 1变异体携带者可表现出提示PD（嗅觉减退）的前驱症状，表现出外周血单核细胞中α-突触核蛋白水平升高，并表现出多巴胺转运蛋白异常。具有较高PD风险的LRRK 2变异携带者可能表现出轻微的运动异常，但没有前驱症状，更高地暴露于某些环境因素（非类固醇抗炎药）和外周炎症特征。这些信息将帮助临床医生定制适当的筛查测试和咨询，并促进研究人员开发预测标志物，疾病修饰治疗和选择可能受益于预防干预措施的健康个体。
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. 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. 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.
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影响因子：
8.6
作者：
Alcalay, Roy N.;Mirelman, Anat;Saunders-Pullman, Rachel;Tang, Ming-X;Mejia Santana, Helen;Raymond, Deborah;Roos, Ernest;Orbe-Reilly, Martha;Gurevich, Tanya;Bar Shira, Anat;Weisz, Mali Gana;Yasinovsky, Kira;Zalis, Maayan;Thaler, Avner;Deik, Andres;Barrett, Matthew James;Cabassa, Jose;Groves, Mark;Hunt, Ann L.;Lubarr, Naomi;San Luciano, Marta;Miravite, Joan;Palmese, Christina;Sachdev, Rivka;Sarva, Harini;Severt, Lawrence;Shanker, Vicki;Swan, Matthew Carrington;Soto-Valencia, Jeannie;Johannes, Brooke;Ortega, Robert;Fahn, Stanley;Cote, Lucien;Waters, Cheryl;Mazzoni, Pietro;Ford, Blair;Louis, Elan;Levy, Oren;Rosado, Llency;Ruiz, Diana;Dorovski, Tsvyatko;Pauciulo, Michael;Nichols, William;Orr-Urtreger, Avi;Ozelius, Laurie;Clark, Lorraine;Giladi, Nir;Bressman, Susan;Marder, Karen S.
通讯作者：
Marder, Karen S.
影响因子：
8.6
作者：
Greuel, Andrea;Trezzi, Jean-Pierre;Eggers, Carsten
通讯作者：
Eggers, Carsten
影响因子：
14.5
作者：
Blauwendraat, Cornelis;Reed, Xylena;Singleton, Andrew B.
通讯作者：
Singleton, Andrew B.
DOI：
10.1002/mds.28496
发表时间：
2021-05
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Avenali M;Cerri S;Ongari G;Ghezzi C;Pacchetti C;Tassorelli C;Valente EM;Blandini F
通讯作者：
Blandini F
DOI：
10.1002/mds.28525
发表时间：
2021-06
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Galper J;Balwani M;Fahn S;Waters C;Krohn L;Gan-Or Z;Dzamko N;Alcalay RN
通讯作者：
Alcalay RN