TY  - JOUR
AU  - Lee, Hwee Ling
AU  - Stirnberg, Rüdiger
AU  - Wu, Sichu
AU  - Wang, Xin
AU  - Stöcker, Tony
AU  - Jung, Sonja
AU  - Montag, Christian
AU  - Axmacher, Nikolai
TI  - Genetic Alzheimer's Disease Risk Affects the Neural Mechanisms of Pattern Separation in Hippocampal Subfields.
JO  - Current biology
VL  - 30
IS  - 21
SN  - 0960-9822
CY  - London
PB  - Current Biology Ltd.
M1  - DZNE-2021-00114
SP  - 4201 - 4212.e3
PY  - 2020
N1  - ISSN 0960-9822 not unique: **3 hits**.
AB  - 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.
KW  - Adult
KW  - Alleles
KW  - Alzheimer Disease: diagnosis
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: physiopathology
KW  - Apolipoproteins E: genetics
KW  - Apolipoproteins E: metabolism
KW  - Brain Mapping
KW  - CA3 Region, Hippocampal: diagnostic imaging
KW  - CA3 Region, Hippocampal: physiopathology
KW  - Dentate Gyrus: diagnostic imaging
KW  - Dentate Gyrus: physiopathology
KW  - Female
KW  - Genetic Predisposition to Disease
KW  - Genotyping Techniques
KW  - Healthy Volunteers
KW  - Heterozygote
KW  - Humans
KW  - Magnetic Resonance Imaging
KW  - Male
KW  - Memory, Episodic
KW  - Risk Factors
KW  - Young Adult
KW  - 7T (Other)
KW  - APOE genotype (Other)
KW  - CA3 (Other)
KW  - dentate gyrus (Other)
KW  - episodic memory (Other)
KW  - functional connectivity (Other)
KW  - hippocampal subfields (Other)
KW  - pattern separation (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:32916120
DO  - DOI:10.1016/j.cub.2020.08.042
UR  - https://pub.dzne.de/record/154260
ER  -