Journal Article

DZNE-2021-00114

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic Alzheimer's Disease Risk Affects the Neural Mechanisms of Pattern Separation in Hippocampal Subfields.

Lee, H. L. (First author)DZNE* ; Stirnberg, R.DZNE* ; Wu, S.DZNE* ; Wang, X.DZNE* ; Stöcker, T.DZNE* ; Jung, S. ; Montag, C. ; Axmacher, N.

2020
Current Biology Ltd. London

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Please use a persistent id in citations: doi:10.1016/j.cub.2020.08.042

Abstract: 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.

Keyword(s): Adult (MeSH) ; Alleles (MeSH) ; Alzheimer Disease: diagnosis (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: physiopathology (MeSH) ; Apolipoproteins E: genetics (MeSH) ; Apolipoproteins E: metabolism (MeSH) ; Brain Mapping (MeSH) ; CA3 Region, Hippocampal: diagnostic imaging (MeSH) ; CA3 Region, Hippocampal: physiopathology (MeSH) ; Dentate Gyrus: diagnostic imaging (MeSH) ; Dentate Gyrus: physiopathology (MeSH) ; Female (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Genotyping Techniques (MeSH) ; Healthy Volunteers (MeSH) ; Heterozygote (MeSH) ; Humans (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Male (MeSH) ; Memory, Episodic (MeSH) ; Risk Factors (MeSH) ; Young Adult (MeSH) ; 7T ; APOE genotype ; CA3 ; dentate gyrus ; episodic memory ; functional connectivity ; hippocampal subfields ; pattern separation

Note: ISSN 0960-9822 not unique: **3 hits**.

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Contributing Institute(s):

1. Patient studies (Patient studies, Bonn)
2. MR Physics (AG Stöcker)
3. Memory and Sleep (AG Axmacher)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)
2. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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