Franzmeier, Nicolai, Ren, Jinyi, Damm, Alexander, Monte-Rubio, Gemma, Boada, Merce, Ruiz, Agustin, Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Jessen, Frank, Duezel, Emrah, Rodriguez Gomez, Octavio, Benzinger, Tammie, Goate, Alison, Karch, Celeste M., Fagan, Anne M., McDade, Eric, Buerger, Katharina, Levin, Johannes ORCID: 0000-0001-5092-4306, Duering, Marco, Dichgans, Martin, Suarez-Calvet, Marc, Haass, Christian, Gordon, Brian A., Lim, Yen Ying ORCID: 0000-0002-0308-5156, Masters, Colin L., Janowitz, Daniel, Catak, Cihan, Wolfsgruber, Steffen, Wagner, Michael ORCID: 0000-0003-2589-6440, Milz, Esther, Moreno-Grau, Sonia, Teipel, Stefan, Grothe, Michel J., Kilimann, Ingo, Rossor, Martin, Fox, Nick, Laske, Christoph, Chhatwal, Jasmeer, Falkai, Peter ORCID: 0000-0003-2873-8667, Perneczky, Robert, Lee, Jae-Hong, Spottke, Annika, Boecker, Henning ORCID: 0000-0003-2346-0598, Brosseron, Frederic, Fliessbach, Klaus, Heneka, Michael T., Nestor, Peter, Peters, Oliver ORCID: 0000-0003-0568-2998, Fuentes, Manuel, Menne, Felix ORCID: 0000-0003-1574-4443, Priller, Josef ORCID: 0000-0001-7596-0979, Spruth, Eike J., Franke, Christiana ORCID: 0000-0002-5609-2472, Schneider, Anja ORCID: 0000-0001-9540-8700, Westerteicher, Christine, Speck, Oliver ORCID: 0000-0002-6019-5597, Wiltfang, Jens, Bartels, Claudia, Araque Caballero, Miguel angel, Metzger, Coraline, Bittner, Daniel, Salloway, Stephen, Danek, Adrian ORCID: 0000-0001-8857-5383, Hassenstab, Jason, Yakushev, Igor ORCID: 0000-0003-4764-798X, Schofield, Peter R., Morris, John C., Bateman, Randall J. and Ewers, Michael (2021). The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer's disease. Mol. Psychiatr., 26 (2). S. 614 - 629. LONDON: SPRINGERNATURE. ISSN 1476-5578

Full text not available from this repository.

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, A beta) 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 A beta, 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 A beta-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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Franzmeier, NicolaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ren, JinyiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Damm, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Monte-Rubio, GemmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boada, MerceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruiz, AgustinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duezel, EmrahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez Gomez, OctavioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzinger, TammieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goate, AlisonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karch, Celeste M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fagan, Anne M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McDade, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buerger, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levin, JohannesUNSPECIFIEDorcid.org/0000-0001-5092-4306UNSPECIFIED
Duering, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dichgans, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suarez-Calvet, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haass, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gordon, Brian A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lim, Yen YingUNSPECIFIEDorcid.org/0000-0002-0308-5156UNSPECIFIED
Masters, Colin L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janowitz, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Catak, CihanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolfsgruber, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Milz, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moreno-Grau, SoniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teipel, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grothe, Michel J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilimann, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossor, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fox, NickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laske, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chhatwal, JasmeerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Falkai, PeterUNSPECIFIEDorcid.org/0000-0003-2873-8667UNSPECIFIED
Perneczky, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Jae-HongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spottke, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boecker, HenningUNSPECIFIEDorcid.org/0000-0003-2346-0598UNSPECIFIED
Brosseron, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fliessbach, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heneka, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nestor, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, OliverUNSPECIFIEDorcid.org/0000-0003-0568-2998UNSPECIFIED
Fuentes, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Menne, FelixUNSPECIFIEDorcid.org/0000-0003-1574-4443UNSPECIFIED
Priller, JosefUNSPECIFIEDorcid.org/0000-0001-7596-0979UNSPECIFIED
Spruth, Eike J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, ChristianaUNSPECIFIEDorcid.org/0000-0002-5609-2472UNSPECIFIED
Schneider, AnjaUNSPECIFIEDorcid.org/0000-0001-9540-8700UNSPECIFIED
Westerteicher, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speck, OliverUNSPECIFIEDorcid.org/0000-0002-6019-5597UNSPECIFIED
Wiltfang, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartels, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Araque Caballero, Miguel angelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metzger, CoralineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bittner, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salloway, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Danek, AdrianUNSPECIFIEDorcid.org/0000-0001-8857-5383UNSPECIFIED
Hassenstab, JasonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yakushev, IgorUNSPECIFIEDorcid.org/0000-0003-4764-798XUNSPECIFIED
Schofield, Peter R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morris, John C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bateman, Randall J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ewers, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-607371
DOI: 10.1038/s41380-019-0404-6
Journal or Publication Title: Mol. Psychiatr.
Volume: 26
Number: 2
Page Range: S. 614 - 629
Date: 2021
Publisher: SPRINGERNATURE
Place of Publication: LONDON
ISSN: 1476-5578
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Biochemistry & Molecular Biology; Neurosciences; PsychiatryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60737

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item