Abstract
| Original language | English |
|---|---|
| Article number | 4899 |
| Journal | Nature communications |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Dec 2022 |
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In: Nature communications, Vol. 13, No. 1, 4899, 01.12.2022.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Earlier Alzheimer’s disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading
AU - Frontzkowski, Lukas
AU - Ewers, Michael
AU - Brendel, Matthias
AU - Biel, Davina
AU - Ossenkoppele, Rik
AU - Hager, Paul
AU - Steward, Anna
AU - Dewenter, Anna
AU - Römer, Sebastian
AU - Rubinski, Anna
AU - Buerger, Katharina
AU - Janowitz, Daniel
AU - Binette, Alexa Pichet
AU - Smith, Ruben
AU - Strandberg, Olof
AU - Carlgren, Niklas Mattsson
AU - Dichgans, Martin
AU - Hansson, Oskar
AU - Franzmeier, Nicolai
N1 - Funding Information: We acknowledge all members of the Alzheimer’s Disease Neuroimaging Initiative. N.F. received research support from the Hertie Foundation (Network of Excellence in Clinical Neurosciences). O.H. has acquired research support (for the institution) from AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, GE Healthcare, Pfizer, and Roche. In the past 2 years, he has received consultancy/speaker fees from Roche, Genentech, Siemens, Biogen, Alzpath, and Cerveau. The BioFINDER study was supported by the Swedish Research Council, the Knut and Alice Wallenberg foundation, the Marianne and Marcus Wallenberg foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, the Parkinson Foundation of Sweden, the Parkinson Research Foundation, the Skåne University Hospital Foundation, and the Swedish federal government under the ALF agreement. Doses of F-flutemetamol injection were sponsored by GE Healthcare. The precursor of F-flortaucipir was provided by AVID Radiopharmaceuticals. ADNI data collection and sharing for this project was funded by the ADNI (National Institutes of Health grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: AbbVie, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Araclon Biotech, BioClinica Inc., Biogen, Bristol-Myers Squibb Company, CereSpir Inc., Cogstate, Eisai Inc., Elan Pharmaceuticals Inc., Eli Lilly and Company, EuroImmun, F. Hoffmann-La Roche Ltd. and its affiliated company Genentech Inc., Fujirebio, GE Healthcare, IXICO Ltd., Janssen Alzheimer Immunotherapy Research and Development LLC., Johnson & Johnson Pharmaceutical Research and Development LLC., Lumosity, Lundbeck, Merck & Co. Inc., Meso Scale Diagnostics LLC., NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer Inc., Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). 18 18 Funding Information: We acknowledge all members of the Alzheimer’s Disease Neuroimaging Initiative. N.F. received research support from the Hertie Foundation (Network of Excellence in Clinical Neurosciences). O.H. has acquired research support (for the institution) from AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, GE Healthcare, Pfizer, and Roche. In the past 2 years, he has received consultancy/speaker fees from Roche, Genentech, Siemens, Biogen, Alzpath, and Cerveau. The BioFINDER study was supported by the Swedish Research Council, the Knut and Alice Wallenberg foundation, the Marianne and Marcus Wallenberg foundation, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, the Parkinson Foundation of Sweden, the Parkinson Research Foundation, the Skåne University Hospital Foundation, and the Swedish federal government under the ALF agreement. Doses of18F-flutemetamol injection were sponsored by GE Healthcare. The precursor of18F-flortaucipir was provided by AVID Radiopharmaceuticals. ADNI data collection and sharing for this project was funded by the ADNI (National Institutes of Health grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: AbbVie, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Araclon Biotech, BioClinica Inc., Biogen, Bristol-Myers Squibb Company, CereSpir Inc., Cogstate, Eisai Inc., Elan Pharmaceuticals Inc., Eli Lilly and Company, EuroImmun, F. Hoffmann-La Roche Ltd. and its affiliated company Genentech Inc., Fujirebio, GE Healthcare, IXICO Ltd., Janssen Alzheimer Immunotherapy Research and Development LLC., Johnson & Johnson Pharmaceutical Research and Development LLC., Lumosity, Lundbeck, Merck & Co. Inc., Meso Scale Diagnostics LLC., NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer Inc., Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - In Alzheimer’s disease (AD), younger symptom onset is associated with accelerated disease progression and tau spreading, yet the mechanisms underlying faster disease manifestation are unknown. To address this, we combined resting-state fMRI and longitudinal tau-PET in two independent samples of controls and biomarker-confirmed AD patients (ADNI/BioFINDER, n = 240/57). Consistent across both samples, we found that younger symptomatic AD patients showed stronger tau-PET in globally connected fronto-parietal hubs, i.e., regions that are critical for maintaining cognition in AD. Stronger tau-PET in hubs predicted faster subsequent tau accumulation, suggesting that tau in globally connected regions facilitates connectivity-mediated tau spreading. Further, stronger tau-PET in hubs mediated the association between younger age and faster tau accumulation in symptomatic AD patients, which predicted faster cognitive decline. These independently validated findings suggest that younger AD symptom onset is associated with stronger tau pathology in brain hubs, and accelerated tau spreading throughout connected brain regions and cognitive decline.
AB - In Alzheimer’s disease (AD), younger symptom onset is associated with accelerated disease progression and tau spreading, yet the mechanisms underlying faster disease manifestation are unknown. To address this, we combined resting-state fMRI and longitudinal tau-PET in two independent samples of controls and biomarker-confirmed AD patients (ADNI/BioFINDER, n = 240/57). Consistent across both samples, we found that younger symptomatic AD patients showed stronger tau-PET in globally connected fronto-parietal hubs, i.e., regions that are critical for maintaining cognition in AD. Stronger tau-PET in hubs predicted faster subsequent tau accumulation, suggesting that tau in globally connected regions facilitates connectivity-mediated tau spreading. Further, stronger tau-PET in hubs mediated the association between younger age and faster tau accumulation in symptomatic AD patients, which predicted faster cognitive decline. These independently validated findings suggest that younger AD symptom onset is associated with stronger tau pathology in brain hubs, and accelerated tau spreading throughout connected brain regions and cognitive decline.
UR - http://www.scopus.com/inward/record.url?scp=85136686870&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-022-32592-7
DO - https://doi.org/10.1038/s41467-022-32592-7
M3 - Article
C2 - 35987901
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4899
ER -