5 documents found, page 1 of 1
Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort
Vollstedt, Eva‐Juliane; Schaake, Susen; Lohmann, Katja; Padmanabhan, Shalini; Brice, Alexis; Lesage, Suzanne; Tesson, Christelle; Vidailhet, MarieBackground: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objectiv...
Genetic associations between modifiable risk factors and Alzheimer disease
Luo, Jiao; Thomassen, Jesper Qvist; Bellenguez, Céline; Grenier-Boley, Benjamin; de Rojas, Itziar; Castillo, Atahualpa; Parveen, KayenatImportance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire n...
Association of rare APOE missense variants V236E and R251G with risk of Alzheim...
Le Guen, Yann; Belloy, Michael E.; Grenier-Boley, Benjamin; de Rojas, Itziar; Castillo-Morales, Atahualpa; Jansen, Iris; Nicolas, AudeImportance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide crit...
A comprehensive study of the genetic impact of rare variants in SORL1 in Europe...
Verheijen, Jan; Van den Bossche, Tobi; van der Zee, Julie; Engelborghs, Sebastiaan; Sanchez-Valle, Raquel; Lladó, Albert; Graff, CarolineThe sortilin-related receptor 1 (SORL1) gene has been associated with increased risk for Alzheimer's disease (AD). Rare genetic variants in the SORL1 gene have also been implicated in autosomal dominant early-onset AD (EOAD). Here we report a large-scale investigation of the contribution of genetic variability in SORL1 to EOAD in a European EOAD cohort. We performed massive parallel amplicon-based re-sequencing...
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a...
Cacace, Rita; Van den Bossche, Tobi; Engelborghs, Sebastiaan; Geerts, Nathalie; Laureys, Annelies; Dillen, Lubina; Graff, Caroline; Thonberg, HåkanRare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N = 261) and control (N = 319) cohort,...