Home > Publications Database > Genetic Alzheimer's Disease Risk Affects the Neural Mechanisms of Pattern Separation in Hippocampal Subfields. > print

001     154260
005     20230915094030.0
024 7 _ |a 10.1016/j.cub.2020.08.042
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024 7 _ |a 0960-9822
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024 7 _ |a 1879-0445
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037 _ _ |a DZNE-2021-00114
041 _ _ |a English
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100 1 _ |a Lee, Hwee Ling
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245 _ _ |a Genetic Alzheimer's Disease Risk Affects the Neural Mechanisms of Pattern Separation in Hippocampal Subfields.
260 _ _ |a London
|c 2020
|b Current Biology Ltd.
336 7 _ |a article
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520 _ _ |a The hippocampal subfields perform distinct operations during acquisition, differentiation, and recollection of episodic memories, and deficits in pattern separation are among the first symptoms of Alzheimer's disease (AD). We investigated how hippocampal subfields contribute to pattern separation and how this is affected by Apolipoprotein-E (APOE), the strongest AD genetic risk factor. Using ultra-high-field (7T) functional magnetic resonance imaging (fMRI), APOE-ε3-ε3 carriers predominantly recruited cornu ammonis 3 (CA3) during a spatial mnemonic discrimination task, whereas APOE-ε3-ε4 and APOE-ε3-ε2 carriers engaged CA3 and dentate gyrus (DG) to the same degree. Specifically, APOE-ε3-ε4 carriers showed reduced pattern separation in CA3, whereas APOE-ε3-ε2 carriers exhibited increased effects in DG and pattern separation-related functional connectivity between DG and CA3. Collectively, these results demonstrate that AD genetic risk alters hemodynamic responses in young pre-symptomatic individuals, paving the way for development of biomarkers for preclinical AD.
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650 _ 7 |a 7T
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650 _ 7 |a APOE genotype
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650 _ 7 |a CA3
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650 _ 7 |a dentate gyrus
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650 _ 7 |a episodic memory
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650 _ 7 |a functional connectivity
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650 _ 7 |a hippocampal subfields
|2 Other
650 _ 7 |a pattern separation
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650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Alleles
|2 MeSH
650 _ 2 |a Alzheimer Disease: diagnosis
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: physiopathology
|2 MeSH
650 _ 2 |a Apolipoproteins E: genetics
|2 MeSH
650 _ 2 |a Apolipoproteins E: metabolism
|2 MeSH
650 _ 2 |a Brain Mapping
|2 MeSH
650 _ 2 |a CA3 Region, Hippocampal: diagnostic imaging
|2 MeSH
650 _ 2 |a CA3 Region, Hippocampal: physiopathology
|2 MeSH
650 _ 2 |a Dentate Gyrus: diagnostic imaging
|2 MeSH
650 _ 2 |a Dentate Gyrus: physiopathology
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Genetic Predisposition to Disease
|2 MeSH
650 _ 2 |a Genotyping Techniques
|2 MeSH
650 _ 2 |a Healthy Volunteers
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650 _ 2 |a Heterozygote
|2 MeSH
650 _ 2 |a Humans
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650 _ 2 |a Magnetic Resonance Imaging
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Memory, Episodic
|2 MeSH
650 _ 2 |a Risk Factors
|2 MeSH
650 _ 2 |a Young Adult
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700 1 _ |a Stirnberg, Rüdiger
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700 1 _ |a Wu, Sichu
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700 1 _ |a Wang, Xin
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700 1 _ |a Stöcker, Tony
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700 1 _ |a Jung, Sonja
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700 1 _ |a Montag, Christian
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700 1 _ |a Axmacher, Nikolai
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773 _ _ |a 10.1016/j.cub.2020.08.042
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