Browsing by Author "Vellas, B."

Now showing 1 - 4 of 4
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    Blood Biomarkers from Research Use to Clinical Practice: What Must Be Done? A Report from the EU/US CTAD Task Force
    (Springer, 2022) Angioni, D.; Delrieu, J.; Hansson, O.; Fillit, H.; Aisen, P.; Cummings, J.; Sim, J. R.; Braunstein, J. B.; Sabbagh, M.; Bittner, T.; Pontecorvo, M.; Bozeat, S.; Dage, J. L.; Largent, E.; Mattke, S.; Correa, O.; Gutierrez Robledo, L. M.; Baldivieso, V.; Willis, D. R.; Atri, A.; Bateman, R. J.; Ousset, P-J.; Vellas, B.; Weiner, M.; Neurology, School of Medicine
    Timely and accurate diagnosis of Alzheimer’s disease (AD) in clinical practice remains challenging. PET and CSF biomarkers are the most widely used biomarkers to aid diagnosis in clinical research but present limitations for clinical practice (i.e., cost, accessibility). Emerging blood-based markers have the potential to be accurate, cost-effective, and easily accessible for widespread clinical use, and could facilitate timely diagnosis. The EU/US CTAD Task Force met in May 2022 in a virtual meeting to discuss pathways to implementation of blood-based markers in clinical practice. Specifically, the CTAD Task Force assessed: the state-of-art for blood-based markers, the current use of blood-based markers in clinical trials, the potential use of blood-based markers in clinical practice, the current challenges with blood-based markers, and the next steps needed for broader adoption in clinical practice.
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    Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease
    (Nature Publishing Group, 2011-11) Furney, SJ; Simmons, A.; Breen, G.; Pedroso, I.; Lunnon, K.; Proitsi, P.; Hodges, A.; Powell, J.; Wahlund, L-O; Kloszewska, I.; Mecocci, P.; Soininen, H.; Tsolaki, M.; Vellas, B.; Spenger, C.; Lathrop, M.; Shen, L.; Kim, S.; Saykin, AJ; Weiner, MW; Lovestone, S.; Alzheimer's Disease Neuroimaging Initiative and the AddNeuroMed Consortium; Radiology and Imaging Sciences, School of Medicine
    Alzheimer's disease (AD) is a progressive neurodegenerative disorder with considerable evidence suggesting an initiation of disease in the entorhinal cortex and hippocampus and spreading thereafter to the rest of the brain. In this study, we combine genetics and imaging data obtained from the Alzheimer's Disease Neuroimaging Initiative and the AddNeuroMed study. To identify genetic susceptibility loci for AD, we conducted a genome-wide study of atrophy in regions associated with neurodegeneration in this condition. We identified one single-nucleotide polymorphism (SNP) with a disease-specific effect associated with entorhinal cortical volume in an intron of the ZNF292 gene (rs1925690; P-value=2.6 × 10(-8); corrected P-value for equivalent number of independent quantitative traits=7.7 × 10(-8)) and an intergenic SNP, flanking the ARPP-21 gene, with an overall effect on entorhinal cortical thickness (rs11129640; P-value=5.6 × 10(-8); corrected P-value=1.7 × 10(-7)). Gene-wide scoring also highlighted PICALM as the most significant gene associated with entorhinal cortical thickness (P-value=6.7 × 10(-6)).
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    Identification of functional variants from whole-exome sequencing, combined with neuroimaging genetics
    (Springer Nature, 2013) Nho, K.; Corneveaux, J. J.; Kim, S.; Lin, H.; Risacher, S. L.; Shen, L.; Swaminathan, S.; Ramanan, V. K.; Liu, Y.; Foroud, T.; Inlow, M. H.; Siniard, A. L.; Reiman, R. A.; Aisen, P. S.; Petersen, R. C.; Green, R. C.; Jack, C. R.; Weiner, M. W.; Baldwin, C. T.; Lunetta, K.; Farrer, L. A.; Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study; Furney, S. J.; Lovestone, S.; Simmons, A.; Mecocci, P.; Vellas, B.; Tsolaki, M.; Kloszewska, I.; Soininen, H.; AddNeuroMed Consortium; McDonald, B. C.; Farlow, M. R.; Ghetti, B.; Indiana Memory and Aging Study; Huentelman, M. J.; Saykin, A. J.; Alzheimer's Disease Neuroimaging Initiative (ADNI); Radiology and Imaging Sciences, School of Medicine
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    Whole-exome sequencing and imaging genetics identify functional variants for rate of change in hippocampal volume in mild cognitive impairment
    (Springer Nature, 2013) Nho, K.; Corneveaux, J. J.; Kim, S.; Lin, H.; Risacher, S. L.; Shen, L.; Swaminathan, S.; Ramanan, V. K.; Liu, Y.; Foroud, T.; Inlow, M. H.; Siniard, A. L.; Reiman, R. A.; Aisen, P. S.; Petersen, R. C.; Green, R. C.; Jack, C. R.; Weiner, M. W.; Baldwin, C. T.; Lunetta, K.; Farrer, L. A.; Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study; Furney, S. J.; Lovestone, S.; Simmons, A.; Mecocci, P.; Vellas, B.; Tsolaki, M.; Kloszewska, I.; Soininen, H.; AddNeuroMed Consortium; McDonald, B. C.; Farlow, M. R.; Ghetti, B.; Indiana Memory and Aging Study; Huentelman, M. J.; Saykin, A. J.; Alzheimer's Disease Neuroimaging Initiative (ADNI); Radiology and Imaging Sciences, School of Medicine
    Whole-exome sequencing of individuals with mild cognitive impairment, combined with genotype imputation, was used to identify coding variants other than the apolipoprotein E (APOE) ε4 allele associated with rate of hippocampal volume loss using an extreme trait design. Matched unrelated APOE ε3 homozygous male Caucasian participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were selected at the extremes of the 2-year longitudinal change distribution of hippocampal volume (eight subjects with rapid rates of atrophy and eight with slow/stable rates of atrophy). We identified 57 non-synonymous single nucleotide variants (SNVs) which were found exclusively in at least 4 of 8 subjects in the rapid atrophy group, but not in any of the 8 subjects in the slow atrophy group. Among these SNVs, the variants that accounted for the greatest group difference and were predicted in silico as 'probably damaging' missense variants were rs9610775 (CARD10) and rs1136410 (PARP1). To further investigate and extend the exome findings in a larger sample, we conducted quantitative trait analysis including whole-brain search in the remaining ADNI APOE ε3/ε3 group (N=315). Genetic variation within PARP1 and CARD10 was associated with rate of hippocampal neurodegeneration in APOE ε3/ε3. Meta-analysis across five independent cross sectional cohorts indicated that rs1136410 is also significantly associated with hippocampal volume in APOE ε3/ε3 individuals (N=923). Larger sequencing studies and longitudinal follow-up are needed for confirmation. The combination of next-generation sequencing and quantitative imaging phenotypes holds significant promise for discovery of variants involved in neurodegeneration.