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BRIDGET: BRain Imaging, cognition, Dementia and next generation GEnomics

Projectomschrijving

Er is tot op heden geen genezing voor de ziekte van Alzheimer mogelijk. Daarom is het belangrijk mogelijkheden te ontwikkelen om de ziekte te voorkomen. Om dit te kunnen doen is het noodzakelijk om mensen, die het hoogste risico op de ziekte lopen, in een vroeg stadium op te sporen. 

Aanpak

In dit project bestuderen de onderzoekers op MRI-scans de vroegste hersenveranderingen die een voorbode zijn van dementie. Ze bestuderen erfelijke risicofactoren en omgevingsfactoren, zoals voeding, beweging en roken en proberen te ontrafelen hoe deze factoren tot vroege hersenveranderingen leiden. 

Samenwerkingspartners

Het consortium bestaat uit onderzoekers van de grootste langlopende bevolkingsonderzoeken in Europa, aangevuld met externe partners uit de Verenigde Staten en Australië. 

Verwachte resultaten

De onderzoeksresultaten zullen nieuwe inzichten geven in de vroegste hersenveranderingen die tot dementie leiden. Ook geven ze meer duidelijkheid over de oorzaak van deze veranderingen. Dit kan de basis vormen voor nieuwe preventieve behandelingen.

Meer informatie

Producten

Titel: Genetic architecture of subcortical brain structures in 38,851 individuals
Auteur: Satizabal, Claudia L., Adams, Hieab H. H., Hibar, Derrek P., White, Charles C., Knol, Maria J., Stein, Jason L., Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V., Smith, Albert V., Bis, Joshua C., Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J., Yang, Jingyun, Yanek, Lisa R., Lee, Tom V., Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D., Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavi
Magazine: Nature Genetics
Titel: Corticosteroids and Regional Variations in Thickness of the Human Cerebral Cortex across the Lifespan
Auteur: Parker, Nadine, Vidal-Pineiro, Didac, French, Leon, Shin, Jean, Adams, Hieab H H, Brodaty, Henry, Cox, Simon R, Deary, Ian J, Fjell, Anders M, Frenzel, Stefan, Grabe, Hans, Hosten, Norbert, Ikram, Mohammad Arfan, Jiang, Jiyang, Knol, Maria J, Mazoyer, Bernard, Mishra, Aniket, Sachdev, Perminder S, Salum, Giovanni, Satizabal, Claudia L, Schmidt, Helena, Schmidt, Reinhold, Seshadri, Sudha, Schumann, Gunter, Völzke, Henry, Walhovd, Kristine B, Wen, Wei, Wittfeld, Katharina, Yang, Qiong, Debette, S
Magazine: Cerebral Cortex
Titel: Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging
Auteur: Knol, Maria J., Heshmatollah, Alis, Cremers, Lotte G.M., Ikram, M. Kamran, Uitterlinden, André G., van Duijn, Cornelia M., Niessen, Wiro J., Vernooij, Meike W., Ikram, M. Arfan, Adams, Hieab H.H.
Magazine: Aging

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Samenvatting van de aanvraag

Establishing efficient prevention strategies for dementia and Alzheimer disease (AD) is a major health priority for the coming years. An important hurdle is that pathological processes leading to AD begin many years before clinical diagnosis, hence efficient prevention should be initiated very early. This requires identifying individuals in the general population who are at high risk of developing dementia and exploring the molecular pathways underlying the structural brain alterations that precede the occurrence of dementia, an essential step for identifying novel relevant drug targets. We propose to explore the genetic and epigenetic determinants of quantitative MRI-markers of brain aging that are powerful predictors of dementia/AD risk, and to examine the clinical significance of the markers in a population-based setting. Leveraging the extensive information collected within the largest European population-based cohort studies with neuroimaging data, we will first search for genetic variants associated with established and novel MRI-markers of brain aging, focusing particularly on rare variants, using both agnostic and candidate locus approaches (loci identified through GWAS of AD or MRI-markers of brain aging). In contrast with GWAS signals, rare variants may lead to the discovery of causal variants, and have hardly been explored in association with structural MRI-markers. Second, we will take an original lifetime perspective, through examination of samples in various age categories spanning from young to older age, many of which with repeated MRI and blood sampling. Indeed, there is increasing evidence that early-life factors play an important role in the occurrence of late-onset neurodegenerative diseases. We propose an innovative exploration of lifetime changes in methylation associated with structural brain alterations using a novel bisulfite sequencing technology, to help identify functional and disease relevant variants. We will also study the modifying effects of vascular risk factors and socio-economic status on genetic/epigenetic determinants of brain aging. Third, we will explore the clinical and functional significance of the genetic and epigenetic markers. We will examine their association with cognitive performance & decline and risk of dementia/AD, capitalizing on elaborate cognitive testing and prospective dementia surveillance. For functional exploration, we will utilize cutting-edge bioinformatic methods, large epigenome maps in multiple tissues including brain, and in vivo experimental verification of predicted molecular mechanisms using established in vivo assays in Drosophila.

Kenmerken

Projectnummer:
733051063
Looptijd: 100%
Looptijd: 100 %
2016
2020
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Prof. dr. M.A. Ikram
Verantwoordelijke organisatie:
Erasmus MC