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Alzheimer's disease...
Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non-demented individuals
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Lorenzini, Luigi (author)
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Collij, Lyduine E. (author)
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Tesi, Niccolo (author)
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show more...
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Vilor-Tejedor, Natalia (author)
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Ingala, Silvia (author)
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Foley, Christopher (author)
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Frisoni, Giovanni B. (author)
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Haller, Sven (author)
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Holstege, Henne (author)
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van der van der Lee, Sven (author)
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Martinez-Lage, Pablo (author)
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Marioni, Riccardo E. (author)
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McCartney, Daniel L. (author)
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O' Brien, John (author)
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Oliveira, Tiago Gil (author)
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Payoux, Pierre (author)
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Reinders, Marcel (author)
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Ritchie, Craig (author)
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Scheltens, Philip (author)
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Schwarz, Adam J. (author)
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Sudre, Carole H. (author)
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Waldman, Adam D. (author)
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Wolz, Robin (author)
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Chatelat, Gael (author)
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Ewers, Michael (author)
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Wink, Alle Meije (author)
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Mutsaerts, Henk J. M. M. (author)
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Gispert, Juan Domingo (author)
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Visser, Pieter Jelle (author)
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Tijms, Betty M. (author)
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Altmann, Andre (author)
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Barkhof, Frederik (author)
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279.
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
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- INTRODUCTION: Unraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, is a key step toward precision medicine. METHODS: We computed pathway-specific genetic risk scores (GRSs) in non-demented individuals and investigated how AD risk variants predict cerebrospinal fluid (CSF) and imaging biomarkers reflecting AD pathology, cardiovascular, white matter integrity, and brain connectivity. RESULTS: CSF amyloidbeta and phosphorylated tau were related to most GRSs. Inflammatory pathways were associated with cerebrovascular disease, whereas quantitative measures of white matter lesion and microstructure integrity were predicted by clearance and migration pathways. Functional connectivity alterations were related to genetic variants involved in signal transduction and synaptic communication. DISCUSSION: This study reveals distinct genetic risk profiles in association with specific pathophysiological aspects in predementia stages of AD, unraveling the biological substrates of the heterogeneity of AD-associated endophenotypes and promoting a step forward in disease understanding and development of personalized therapies. Highlights Polygenic risk for Alzheimer's disease encompasses six biological pathways that can be quantified with pathway-specific genetic risk scores, and differentially relate to cerebrospinal fluid and imaging biomarkers. Inflammatory pathways are mostly related to cerebrovascular burden. White matter health is associated with pathways of clearance and membrane integrity, whereas functional connectivity measures are related to signal transduction and synaptic communication pathways.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- biological pathways
- magnetic resonance imaging
- polygenic risk
- preclinical Alzheimer's disease
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lorenzini, Luigi
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Collij, Lyduine ...
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Tesi, Niccolo
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Vilor-Tejedor, N ...
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Ingala, Silvia
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Blennow, Kaj, 19 ...
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show more...
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Foley, Christoph ...
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Frisoni, Giovann ...
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Haller, Sven
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Holstege, Henne
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van der van der ...
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Martinez-Lage, P ...
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Marioni, Riccard ...
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McCartney, Danie ...
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O' Brien, John
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Oliveira, Tiago ...
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Payoux, Pierre
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Reinders, Marcel
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Ritchie, Craig
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Scheltens, Phili ...
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Schwarz, Adam J.
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Sudre, Carole H.
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Waldman, Adam D.
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Wolz, Robin
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Chatelat, Gael
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Ewers, Michael
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Wink, Alle Meije
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Mutsaerts, Henk ...
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Gispert, Juan Do ...
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Visser, Pieter J ...
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Tijms, Betty M.
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Altmann, Andre
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Barkhof, Frederi ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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ALZHEIMERS & DEM ...
- By the university
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University of Gothenburg
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Karolinska Institutet