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000141083 1001_ $$0P:(DE-HGF)0$$aFranzmeier, Nicolai$$b0
000141083 245__ $$aThe BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer's disease.
000141083 260__ $$aLondon$$bMacmillan$$c2021
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000141083 520__ $$aIn 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.
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000141083 7001_ $$0P:(DE-HGF)0$$aHassenstab, Jason$$b62
000141083 7001_ $$0P:(DE-HGF)0$$aYakushev, Igor$$b63
000141083 7001_ $$0P:(DE-HGF)0$$aSchofield, Peter R$$b64
000141083 7001_ $$0P:(DE-HGF)0$$aMorris, John C$$b65
000141083 7001_ $$0P:(DE-HGF)0$$aBateman, Randall J$$b66
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000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neurobiolaging.2013.05.006$$o10.1016/j.neurobiolaging.2013.05.006
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pone.0086498$$o10.1371/journal.pone.0086498
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/mp.2014.123$$o10.1038/mp.2014.123
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/aww200$$o10.1093/brain/aww200
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/ana.25299$$o10.1002/ana.25299
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neubiorev.2012.07.002$$o10.1016/j.neubiorev.2012.07.002
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neubiorev.2014.03.011$$o10.1016/j.neubiorev.2014.03.011
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3988/jcn.2017.13.4.387$$o10.3988/jcn.2017.13.4.387
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/archneur.64.10.1482$$o10.1001/archneur.64.10.1482
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.0308627101$$o10.1073/pnas.0308627101
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1212/WNL.0000000000001575$$o10.1212/WNL.0000000000001575
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.0708803104$$o10.1073/pnas.0708803104
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.jalz.2014.02.007$$o10.1016/j.jalz.2014.02.007
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2014.01.026$$o10.1016/j.neuron.2014.01.026
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/alzrt213$$o10.1186/alzrt213
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awv338$$o10.1093/brain/awv338
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/jamaneurol.2014.1654$$o10.1001/jamaneurol.2014.1654
000141083 999C5 $$2Crossref$$oO Rodriguez-Gomez 2017$$y2017
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/s13195-017-0314-2$$o10.1186/s13195-017-0314-2
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1056/NEJMoa1202753$$o10.1056/NEJMoa1202753
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awy008$$o10.1093/brain/awy008
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/scitranslmed.aag1767$$o10.1126/scitranslmed.aag1767
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1073/pnas.1317918110$$o10.1073/pnas.1317918110
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3233/JAD-160722$$o10.3233/JAD-160722
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/acn3.274$$o10.1002/acn3.274
000141083 999C5 $$2Crossref$$oP Lozoya-Delgado 2012$$y2012
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pone.0076436$$o10.1371/journal.pone.0076436
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.2967/jnumed.111.089730$$o10.2967/jnumed.111.089730
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/s41598-018-21644-y$$o10.1038/s41598-018-21644-y
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/0022-3956(75)90026-6$$o10.1016/0022-3956(75)90026-6
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1080/09084282.2012.689267$$o10.1080/09084282.2012.689267
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s11682-016-9599-1$$o10.1007/s11682-016-9599-1
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1212/WNL.0000000000003711$$o10.1212/WNL.0000000000003711
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.23-17-06690.2003$$o10.1523/JNEUROSCI.23-17-06690.2003
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S1474-4422(18)30028-0$$o10.1016/S1474-4422(18)30028-0
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neurobiolaging.2015.08.007$$o10.1016/j.neurobiolaging.2015.08.007
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/BF01406373$$o10.1007/BF01406373
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awt094$$o10.1093/brain/awt094
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/cercor/bhp223$$o10.1093/cercor/bhp223
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuropsychologia.2009.02.028$$o10.1016/j.neuropsychologia.2009.02.028
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/hipo.10114$$o10.1002/hipo.10114
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.1778-08.2008$$o10.1523/JNEUROSCI.1778-08.2008
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1146/annurev-neuro-071714-034111$$o10.1146/annurev-neuro-071714-034111
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuroimage.2005.12.033$$o10.1016/j.neuroimage.2005.12.033
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neurobiolaging.2016.04.018$$o10.1016/j.neurobiolaging.2016.04.018
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.jpsychires.2009.09.003$$o10.1016/j.jpsychires.2009.09.003
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/archpsyc.62.4.379$$o10.1001/archpsyc.62.4.379
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1098/rstb.2013.0152$$o10.1098/rstb.2013.0152
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1212/WNL.0000000000003980$$o10.1212/WNL.0000000000003980
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.4736-08.2009$$o10.1523/JNEUROSCI.4736-08.2009
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1371/journal.pone.0005424$$o10.1371/journal.pone.0005424
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1017/S1041610217001284$$o10.1017/S1041610217001284
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S1053-8119(03)00002-8$$o10.1016/S1053-8119(03)00002-8
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/jamaneurol.2016.1236$$o10.1001/jamaneurol.2016.1236
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awy053$$o10.1093/brain/awy053
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/alzrt59$$o10.1186/alzrt59
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00415-012-6481-y$$o10.1007/s00415-012-6481-y
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1001/archneurol.2009.285$$o10.1001/archneurol.2009.285
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nm0498-452$$o10.1038/nm0498-452
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00415-005-0019-5$$o10.1007/s00415-005-0019-5
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-006-0127-z$$o10.1007/s00401-006-0127-z
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.3263-16.2017$$o10.1523/JNEUROSCI.3263-16.2017
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/ana.24517$$o10.1002/ana.24517
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1155/2017/4716197$$o10.1155/2017/4716197
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1460-9568.2004.03720.x$$o10.1111/j.1460-9568.2004.03720.x
000141083 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrneurol.2009.54$$o10.1038/nrneurol.2009.54