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@ARTICLE{Lee:154260,
author = {Lee, Hwee Ling and Stirnberg, Rüdiger and Wu, Sichu and
Wang, Xin and Stöcker, Tony and Jung, Sonja and Montag,
Christian and Axmacher, Nikolai},
title = {{G}enetic {A}lzheimer's {D}isease {R}isk {A}ffects the
{N}eural {M}echanisms of {P}attern {S}eparation in
{H}ippocampal {S}ubfields.},
journal = {Current biology},
volume = {30},
number = {21},
issn = {0960-9822},
address = {London},
publisher = {Current Biology Ltd.},
reportid = {DZNE-2021-00114},
pages = {4201 - 4212.e3},
year = {2020},
note = {ISSN 0960-9822 not unique: **3 hits**.},
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.},
keywords = {Adult / Alleles / Alzheimer Disease: diagnosis / Alzheimer
Disease: genetics / Alzheimer Disease: physiopathology /
Apolipoproteins E: genetics / Apolipoproteins E: metabolism
/ Brain Mapping / CA3 Region, Hippocampal: diagnostic
imaging / CA3 Region, Hippocampal: physiopathology / Dentate
Gyrus: diagnostic imaging / Dentate Gyrus: physiopathology /
Female / Genetic Predisposition to Disease / Genotyping
Techniques / Healthy Volunteers / Heterozygote / Humans /
Magnetic Resonance Imaging / Male / Memory, Episodic / Risk
Factors / Young Adult / 7T (Other) / APOE genotype (Other) /
CA3 (Other) / dentate gyrus (Other) / episodic memory
(Other) / functional connectivity (Other) / hippocampal
subfields (Other) / pattern separation (Other)},
cin = {Patient studies, Bonn / AG Stöcker / AG Axmacher},
ddc = {570},
cid = {I:(DE-2719)1011101 / I:(DE-2719)1013026 /
I:(DE-2719)5000027},
pnm = {344 - Clinical and Health Care Research (POF3-344) / 345 -
Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32916120},
doi = {10.1016/j.cub.2020.08.042},
url = {https://pub.dzne.de/record/154260},
}