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@ARTICLE{Franzmeier:141083,
author = {Franzmeier, Nicolai and Ren, Jinyi and Damm, Alexander and
Monté-Rubio, Gemma and Boada, Mercè and Ruiz, Agustín and
Ramirez, Alfredo and Jessen, Frank and Düzel, Emrah and
Rodríguez Gómez, Octavio and Benzinger, Tammie and Goate,
Alison and Karch, Celeste M and Fagan, Anne M and McDade,
Eric and Bürger, Katharina and Levin, Johannes and Duering,
Marco and Dichgans, Martin and Suárez-Calvet, Marc and
Haass, Christian and Gordon, Brian A and Lim, Yen Ying and
Masters, Colin L and Janowitz, Daniel and Catak, Cihan and
Wolfsgruber, Steffen and Wagner, Michael and Milz, Esther
and Moreno-Grau, Sonia and Teipel, Stefan and Grothe, Michel
J and Kilimann, Ingo and Rossor, Martin and Fox, Nick and
Laske, Christoph and Chhatwal, Jasmeer and Falkai, Peter and
Perneczky, Robert and Lee, Jae-Hong and Spottke, Annika and
Boecker, Henning and Brosseron, Frederic and Fließbach,
Klaus and Heneka, Michael T and Nestor, Peter and Peters,
Oliver and Fuentes Casan, Manuel and Menne, Felix and
Priller, Josef and Spruth, Eike J and Franke, Christiana and
Schneider, Anja and Westerteicher, Christine and Speck,
Oliver and Wiltfang, Jens and Bartels, Claudia and Araque
Caballero, Miguel Ángel and Metzger, Coraline and Bittner,
Daniel and Salloway, Stephen and Danek, Adrian and
Hassenstab, Jason and Yakushev, Igor and Schofield, Peter R
and Morris, John C and Bateman, Randall J and Ewers,
Michael},
title = {{T}he {BDNFV}al66{M}et {SNP} modulates the association
between beta-amyloid and hippocampal disconnection in
{A}lzheimer's disease.},
journal = {Molecular psychiatry},
volume = {26},
number = {2},
issn = {1359-4184},
address = {London},
publisher = {Macmillan},
reportid = {DZNE-2020-07405},
pages = {614-628},
year = {2021},
abstract = {In Alzheimer's disease (AD), a single-nucleotide
polymorphism in the gene encoding brain-derived neurotrophic
factor (BDNFVal66Met) is associated with worse impact of
primary AD pathology (beta-amyloid, Aβ) on
neurodegeneration and cognitive decline, rendering
BDNFVal66Met an important modulating factor of cognitive
impairment in AD. However, the effect of BDNFVal66Met on
functional networks that may underlie cognitive impairment
in AD is poorly understood. Using a cross-validation
approach, we first explored in subjects with autosomal
dominant AD (ADAD) from the Dominantly Inherited Alzheimer
Network (DIAN) the effect of BDNFVal66Met on resting-state
fMRI assessed functional networks. In seed-based
connectivity analysis of six major large-scale networks, we
found a stronger decrease of hippocampus (seed) to
medial-frontal connectivity in the BDNFVal66Met carriers
compared to BDNFVal homozogytes. BDNFVal66Met was not
associated with connectivity in any other networks. Next, we
tested whether the finding of more pronounced decrease in
hippocampal-medial-frontal connectivity in BDNFVal66Met
could be also found in elderly subjects with sporadically
occurring Aβ, including a group with subjective cognitive
decline (N = 149, FACEHBI study) and a group ranging
from preclinical to AD dementia (N = 114, DELCODE
study). In both of these independently recruited groups,
BDNFVal66Met was associated with a stronger effect of more
abnormal Aβ-levels (assessed by biofluid-assay or
amyloid-PET) on hippocampal-medial-frontal connectivity
decreases, controlled for hippocampus volume and other
confounds. Lower hippocampal-medial-frontal connectivity was
associated with lower global cognitive performance in the
DIAN and DELCODE studies. Together these results suggest
that BDNFVal66Met is selectively associated with a higher
vulnerability of hippocampus-frontal connectivity to primary
AD pathology, resulting in greater AD-related cognitive
impairment.},
cin = {AG Jessen / AG Düzel / AG Höglinger 1 / AG Levin / AG
Haass / AG Wagner / AG Teipel / AG Jucker / Patient Studies
Bonn / AG Boecker / AG Heneka ; AG Heneka / AG Nestor / AG
Endres / Clinical Dementia Research Bonn / AG Wiltfang / AG
Müller / Delcode},
ddc = {610},
cid = {I:(DE-2719)1011102 / I:(DE-2719)5000006 /
I:(DE-2719)1110002 / I:(DE-2719)1111016 / I:(DE-2719)1110007
/ I:(DE-2719)1011201 / I:(DE-2719)1510100 /
I:(DE-2719)1210001 / I:(DE-2719)1011101 / I:(DE-2719)1011202
/ I:(DE-2719)1011303 / I:(DE-2719)1310001 /
I:(DE-2719)1811005 / I:(DE-2719)1011305 / I:(DE-2719)1410006
/ I:(DE-2719)1310003 / I:(DE-2719)5000034},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
- Clinical and Health Care Research (POF3-344) / 352 -
Disease Mechanisms (POF4-352) / 354 - Disease Prevention and
Healthy Aging (POF4-354) / 353 - Clinical and Health Care
Research (POF4-353)},
pid = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344 /
G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-354 /
G:(DE-HGF)POF4-353},
experiment = {EXP:(DE-2719)DELCODE-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30899092},
pmc = {pmc:PMC6754794},
doi = {10.1038/s41380-019-0404-6},
url = {https://pub.dzne.de/record/141083},
}