Myers, Nicholas, Pasquini, Lorenzo ORCID: 0000-0002-7899-7061, Goettler, Jens, Grimmer, Timo, Koch, Kathrin, Ortner, Marion, Neitzel, Julia, Muehlau, Mark, Foerster, Stefan, Kurz, Alexander, Foerstl, Hans, Zimmer, Claus, Wohlschlaeger, Afra M., Riedl, Valentin ORCID: 0000-0002-2861-8449, Drzezga, Alexander and Sorg, Christian (2014). Within-patient correspondence of amyloid-beta and intrinsic network connectivity in Alzheimer's disease. Brain, 137. S. 2052 - 2065. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

There is striking overlap between the spatial distribution of amyloid-beta pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-beta and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-beta plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-beta exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-beta on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-beta and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-beta on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-beta distributions. Here we compared spatial patterns of amyloid-beta-plaques (measured by Pittsburgh compound B positron emission tomography) and intrinsic functional connectivity (measured by resting-state functional magnetic resonance imaging) in patients with prodromal Alzheimer's disease via spatial correlations in intrinsic networks covering fronto-parietal heteromodal cortices. At the global network level, we found that amyloid-beta and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-beta aggregates in areas of high intrinsic connectivity on a within-network basis. Further, we saw an internetwork gradient of the magnitude of correlation that depended on network plaque-load. After accounting for this globally positive correlation, local amyloid-beta-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-beta pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-beta-plaque concentration. The local negative association between amyloid-beta and intrinsic connectivity was much more pronounced than conventional group comparisons of intrinsic connectivity would suggest. Our findings indicate that the negative impact of amyloid-beta on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-beta and intrinsic connectivity, with the distribution of amyloid-beta pathology following functional connectivity gradients within and across intrinsic networks.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Myers, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasquini, LorenzoUNSPECIFIEDorcid.org/0000-0002-7899-7061UNSPECIFIED
Goettler, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grimmer, TimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortner, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neitzel, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muehlau, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foerster, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurz, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foerstl, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmer, ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wohlschlaeger, Afra M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riedl, ValentinUNSPECIFIEDorcid.org/0000-0002-2861-8449UNSPECIFIED
Drzezga, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sorg, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-435185
DOI: 10.1093/brain/awu103
Journal or Publication Title: Brain
Volume: 137
Page Range: S. 2052 - 2065
Date: 2014
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2156
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DEFAULT-MODE NETWORK; INDEPENDENT COMPONENT ANALYSIS; MILD COGNITIVE IMPAIRMENT; RESTING-STATE NETWORKS; FUNCTIONAL CONNECTIVITY; BRAIN ACTIVITY; CORTICAL HUBS; DEPOSITION; MRI; DEMENTIAMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43518

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