| 1. |
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| 2. |
- Lambert, Jean-Charles, et al.
(author)
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The CALHM1 P86L Polymorphism is a Genetic Modifier of Age at Onset in Alzheimer's Disease : a Meta-Analysis Study
- 2010
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 22:1, s. 247-255
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Journal article (peer-reviewed)abstract
- The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the epsilon 4 allele of the APOE gene.
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| 3. |
- Boersen, Ronald, et al.
(author)
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Chatterbox: an interactive system of gibberish agents
- 2020
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In: Proceedings of 26th International Symposium of Electronic Arts (ISEA 2020). - 9782981641328
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Conference paper (peer-reviewed)abstract
- We present the interactive multi-agent system Chatterbox, as part of the sound art installation Translanguaging, exploring the notion of translanguaging as a mediation of multilingual and intercultural communication. We discuss the act of languaging as a dual process comprising both semantic language communication, as well as paralanguage that relates to the affective, personal, and cultural aspects related to translanguaging. Through the creation of the Chatterbox agent, generating gibberish vocal streams devoid of semantic content, we aim at highlighting the paralinguistic dimension of languaging. The agent model comprises a kind of gradient map, clustering a segmented corpus of vocal sounds in the latent space of a self-organized map, according to its paralinguistic fingerprint. We utilize Factor Oracles for the creative generation of novel utterances of paralanguaging gibberish by the agent. Incorporating simple subsumption architecture inspired rules, we further moderate the interaction between the gibberish agents, creating rich and complex multi-agent behavior in “paralanguaging discussion”. We outline the artistic and technical considerations in developing our Chatterbox agent throughout the paper. We share several observations made throughout the process of creating the Chatterbox agent, highlighting some of the connections between the notion of (trans)languaging and the implementation of our model.
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| 4. |
- Dubois, Bruno, et al.
(author)
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Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria.
- 2014
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In: Lancet neurology. - 1474-4465. ; 13:6, s. 614-29
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Research review (peer-reviewed)abstract
- In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.
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| 5. |
- Dumanski, Jan P., et al.
(author)
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Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease
- 2016
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 98:6, s. 1208-1219
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Journal article (peer-reviewed)abstract
- Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females.
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| 6. |
- Escott-Price, Valentina, et al.
(author)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Journal article (peer-reviewed)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 7. |
- Goumidi, Louisa, et al.
(author)
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Study of estrogen receptor-α and receptor-β gene polymorphisms on Alzheimer's disease.
- 2011
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 26:3, s. 431-9
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Journal article (peer-reviewed)abstract
- Estrogen treatment can modulate the risk for developing dementia in women. Therefore, single nucleotide polymorphisms (SNPs) in the estrogen receptor genes may constitute genetic susceptibility factors to Alzheimer's disease (AD). Thus, we investigated the impact of the genetic variability of the estrogen receptor α 1 (ESR1) and estrogen receptor α 2 (ESR2) genes on late onset AD risk. We analyzed 39 SNPs in ESR1 and 5 SNPs in ESR2 in a French case-control study of sporadic AD (1007 cases/647 controls). Individuals carrying the minor allele of rs7450824 had a lower risk of AD than homozygous subjects for the major allele (age, gender, and APOE ε4 allele adjusted odds ratio = 0.71 [0.57-0.89], p = 0.003). However, this association did not resist Bonferroni correction for multiple testing (p-threshold < 0.001). Consistently, no significant association could be detected when considering age of onset. We also tested for possible interactions between the ESR SNPs and APOE status (ε4 allele) or gender but no significant interaction could be observed. Even after stratifying the sample on APOE status or gender, no significant association with AD risk could be detected. Finally, we searched for potential gene-gene interactions between ESR1 and ESR2 SNPs but no significant interaction could be detected. Our results reinforce the notion that SNPs in the ESR1 or ESR2 genes do not seem to play a major role in the genetic susceptibility of AD.
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| 8. |
- Jansen, Iris E, et al.
(author)
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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
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In: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
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Journal article (peer-reviewed)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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| 9. |
- Jones, Lesley, et al.
(author)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Journal article (peer-reviewed)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 10. |
- Le Guen, Yann, et al.
(author)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
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Journal article (peer-reviewed)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 11. |
- Luo, Jiao, et al.
(author)
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Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease
- 2023
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In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:5
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Journal article (peer-reviewed)abstract
- IMPORTANCE 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 new drug targeting and improved prevention.DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022.EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors.RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]).CONCLUSIONS AND RELEVANCE This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
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| 12. |
- Prpa, Mirjana, et al.
(author)
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Attending to Breath: Exploring How the Cues in a Virtual Environment Guide the Attention to Breath and Shape the Quality of Experience to Support Mindfulness
- 2018
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In: DIS 2018 - Proceedings of the 2018 Designing Interactive Systems Conference. - New York, NY, USA : ACM. - 9781450351980
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Conference paper (peer-reviewed)abstract
- Busy daily lives and ongoing distractions often make people feel disconnected from their bodies and experiences. Guided attention to self can alleviate this disconnect as in focused-attention meditation, in which breathing often constitutes the primary object on which to focus attention. In this context, sustained breath awareness plays a crucial role in the emergence of the meditation experience. We designed an immersive virtual environment (iVE) with a generative soundtrack that supports sustained attention on breathing by employing the users' breathing in interaction. Both sounds and visuals are directly mapped to the user's breathing patterns, thus bringing the awareness researched. We conducted micro-phenomenology interviews to unfold the process in which breath awareness can be induced and sustained in this environment. The findings revealed the mechanisms by which audio and visual cues in VR can elicit and foster breath-awareness, and unfolded the nuances of this process through subjective experiences of the study participants. Finally, the results emphasize the important role that a sense of agency and control have in shaping the overall quality of the experience. This can in turn inform the design specifications of future mindfulness-based designs focused on breath awareness.
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| 13. |
- Prpa, Mirjana, et al.
(author)
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Respire: a Breath Away from the Experience in Virtual Environment
- 2018
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In: Conference on Human Factors in Computing Systems - Proceedings. - New York, NY, USA : ACM.
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Conference paper (peer-reviewed)abstract
- Respire is a virtual environment presented on a head-mounted display with generative sound built upon our previous work Pulse Breath Water. The system follows the changes in user's breathing patterns upon which it generates changes in the audio and virtual environment. The piece is built upon mindfulness-based design principles with a focus on the breath as a primary object of the user's attention, and employs various approaches to augmenting breathing in the virtual environment.
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| 14. |
- Prpa, Mirjana, et al.
(author)
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The Pulse Breath Water System: Exploring Breathing as an Embodied Interaction for Enhancing the Affective Potential of Virtual Reality
- 2017
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In: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. ; 10280
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Conference paper (peer-reviewed)abstract
- We introduce Pulse Breath Water, an immersive virtual environment (VE) with affect estimation in sound. We employ embodied interaction between a user and the system through the user’s breathing frequencies mapped to the system’s behaviour. In this study we investigate how two different mappings (metaphoric, and “reverse”) of embodied interaction design might enhance the affective properties of the presented system. We build on previous work in embodied cognition, embodied interaction, and affect estimation in sound by examining the impact of affective audiovisuals and two kinds of interaction mapping on the user’s engagement, affective states, and overall experience. The insights gained through questionnaires and semi-structured interviews are discussed in the context of participants’ lived experience and the limitations of the system to be addressed in future work.
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| 15. |
- Tatar, Kivanc, 1988, et al.
(author)
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Latent Timbre Synthesis: Audio-based Variational Auto-Encoders for Music Composition Applications
- 2020
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In: Neural Computing and Applications. - : Springer Science and Business Media LLC. - 0941-0643 .- 1433-3058. ; 33:The Special Issue of Neural Computing and Applications: “Networks in Art, Sound and Design.”, s. 67-84
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Journal article (peer-reviewed)abstract
- We present the Latent Timbre Synthesis, a new audio synthesis method using deep learning. The synthesis method allows composers and sound designers to interpolate and extrapolate between the timbre of multiple sounds using the latent space of audio frames. We provide the details of two Variational Autoencoder architectures for the Latent Timbre Synthesis and compare their advantages and drawbacks. The implementation includes a fully working application with a graphical user interface, called interpolate_two, which enables practitioners to generate timbres between two audio excerpts of their selection using interpolation and extrapolation in the latent space of audio frames. Our implementation is open source, and we aim to improve the accessibility of this technology by providing a guide for users with any technical background. Our study includes a qualitative analysis where nine composers evaluated the Latent Timbre Synthesis and the interpolate_two application within their practices. 2.14.0.0
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| 16. |
- Tatar, Kivanc, 1988, et al.
(author)
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Respire: Virtual Reality Art with Musical Agent Guided by Respiratory Interaction
- 2019
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In: Leonardo Music Journal. - : MIT Press - Journals. - 0961-1215 .- 1531-4812. ; 29, s. 19-24
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Journal article (peer-reviewed)abstract
- Respire is an immersive art piece that brings together three components: an immersive virtual reality (VR) environment, embodied interaction (via a breathing sensor) and a musical agent system to generate unique experiences of augmented breathing. The breathing sensor controls the user’s vertical elevation of the point of view under and over the virtual ocean. The frequency and patterns of breathing data guide the arousal of the musical agent, and the waviness of a virtual ocean in the environment. Respire proposes an intimate exploration of breathing through an intelligent mapping of breathing data to the parameters of visual and sonic environments.
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| 17. |
- Thierry, Gaelle, et al.
(author)
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Molecular characterization of 1q44 microdeletion in 11 patients reveals three candidate genes for intellectual disability and seizures
- 2012
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In: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 158A:7, s. 1633-1640
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Journal article (peer-reviewed)abstract
- Patients with a submicroscopic deletion at 1q43q44 present with intellectual disability (ID), microcephaly, craniofacial anomalies, seizures, limb anomalies, and corpus callosum abnormalities. However, the precise relationship between most of deleted genes and the clinical features in these patients still remains unclear. We studied 11 unrelated patients with 1q44 microdeletion. We showed that the deletions occurred de novo in all patients for whom both parents' DNA was available (10/11). All patients presented with moderate to severe ID, seizures and non-specific craniofacial anomalies. By oligoarray-based comparative genomic hybridization (aCGH) covering the 1q44 region at a high resolution, we obtained a critical deleted region containing two coding genesHNRNPU and FAM36Aand one non-coding geneNCRNA00201. All three genes were expressed in different normal human tissues, including in human brain, with highest expression levels in the cerebellum. Mutational screening of the HNRNPU and FAM36A genes in 191 patients with unexplained isolated ID did not reveal any deleterious mutations while the NCRNA00201 non-coding gene was not analyzed. Nine of the 11 patients did not present with microcephaly or corpus callosum abnormalities and carried a small deletion containing HNRNPU, FAM36A, and NCRNA00201 but not AKT3 and ZNF238, two centromeric genes. These results suggest that HNRNPU, FAM36A, and NCRNA00201 are not major genes for microcephaly and corpus callosum abnormalities but are good candidates for ID and seizures.
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