Universität zu Köln

Seemiller, Joseph ORCID: 0000-0001-7742-8759, Bischof, Gerard N., Hoenig, Merle C., Tahmasian, Masoud ORCID: 0000-0003-3999-3807, van Eimeren, Thilo ORCID: 0000-0002-6951-2325 and Drzezga, Alexander ORCID: 0000-0001-6018-716X (2021). Indication of retrograde tau spreading along Braak stages and functional connectivity pathways. Eur. J. Nucl. Med. Mol. Imaging, 48 (7). S. 2272 - 2283. NEW YORK: SPRINGER. ISSN 1619-7089

Full text not available from this repository.

Abstract

Purpose Tau pathology progression in Alzheimer's disease (AD) is explained through the network degeneration hypothesis and the neuropathological Braak stages; however, the compatibility of these models remains unclear. Methods We utilized [18F]AV-1451 tau-PET scans of 39 subjects with AD and 39 sex-matched amyloid-negative healthy controls (HC) in the ADNI (Alzheimer's Disease Neuroimaging Initiative) dataset. The peak cluster of tau-tracer uptake was identified in each Braak stage of neuropathological tau deposition and used to create a seed-based functional connectivity network (FCN) using 198 HC subjects, to identify healthy networks unaffected by neurodegeneration. Results Voxel-wise tau deposition was both significantly higher inside relative to outside FCNs and correlated significantly and positively with levels of healthy functional connectivity. Within many isolated Braak stages and regions, the correlation between tau and intrinsic functional connectivity was significantly stronger than it was across the whole brain. In this way, each peak cluster of tau was related to multiple Braak stages traditionally associated with both earlier and later stages of disease. Conclusion We show specificity of healthy FCN topography for AD-pathological tau as well as positive voxel-by-voxel correlations between pathological tau and healthy functional connectivity. We propose a model of up- and downstream functional tau progression, suggesting that tau pathology evolves along functional connectivity networks not only downstream (i.e., along the expected sequence of the established Braak stages) but also in part upstream or retrograde (i.e., against the expected sequence of the established Braak stages), with pathology in earlier Braak stages intensified by its functional relationship to later disease stages.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Seemiller, Joseph UNSPECIFIED orcid.org/0000-0001-7742-8759 UNSPECIFIED Bischof, Gerard N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoenig, Merle C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tahmasian, Masoud UNSPECIFIED orcid.org/0000-0003-3999-3807 UNSPECIFIED van Eimeren, Thilo UNSPECIFIED orcid.org/0000-0002-6951-2325 UNSPECIFIED Drzezga, Alexander UNSPECIFIED orcid.org/0000-0001-6018-716X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-591649
DOI:	10.1007/s00259-020-05183-1
Journal or Publication Title:	Eur. J. Nucl. Med. Mol. Imaging
Volume:	48
Number:	7
Page Range:	S. 2272 - 2283
Date:	2021
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1619-7089
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59164