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Brain. 2014 Jul;137(Pt 7):2052-64. doi: 10.1093/brain/awu103. Epub 2014 Apr 26.

Within-patient correspondence of amyloid-β and intrinsic network connectivity in Alzheimer's disease.

Author information

1
1 Department of Neuroradiology, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany2 TUM-Neuroimaging Centre, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany3 Department of Experimental Psychology, Oxford University, 9 South Parks Road, Oxford OX1 3UD, UK nicholas.myers@psy.ox.ac.uk.
2
1 Department of Neuroradiology, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany2 TUM-Neuroimaging Centre, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany.
3
4 Department of Psychiatry, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany.
4
2 TUM-Neuroimaging Centre, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany5 Department of Neurology of Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany.
5
2 TUM-Neuroimaging Centre, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany6 Department of Nuclear Medicine, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany.
6
1 Department of Neuroradiology, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany.
7
1 Department of Neuroradiology, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany2 TUM-Neuroimaging Centre, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany6 Department of Nuclear Medicine, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany.
8
6 Department of Nuclear Medicine, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany7 Department of Nuclear Medicine, University of Cologne, Kerpener Straße 62, 50937 Köln, Germany.
9
1 Department of Neuroradiology, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany2 TUM-Neuroimaging Centre, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany4 Department of Psychiatry, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany.

Abstract

There is striking overlap between the spatial distribution of amyloid-β 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-β and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-β 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-β exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-β on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-β and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-β on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-β distributions. Here we compared spatial patterns of amyloid-β-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-β and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-β 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-β-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-β pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-β-plaque concentration. The local negative association between amyloid-β 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-β on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-β and intrinsic connectivity, with the distribution of amyloid-β pathology following functional connectivity gradients within and across intrinsic networks.

KEYWORDS:

Alzheimer’s disease; PiB-PET; amyloid-β plaques; intrinsic connectivity; resting-state functional MRI

PMID:
24771519
PMCID:
PMC4065018
DOI:
10.1093/brain/awu103
[Indexed for MEDLINE]
Free PMC Article

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