Abstract

In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that tau spreads across connected neurons in an activity-dependent manner. Supporting this, cross-sectional AD studies show that tau deposition patterns resemble functional brain networks. However, whether higher functional connectivity is associated with higher rates of tau accumulation is unclear. Here, we combine resting-state fMRI with longitudinal tau-PET in two independent samples including 53 (ADNI) and 41 (BioFINDER) amyloid-biomarker defined AD subjects and 28 (ADNI) vs. 16 (BioFINDER) amyloid-negative healthy controls. In both samples, AD subjects show faster tau accumulation than controls. Second, in AD, higher fMRI-assessed connectivity between 400 regions of interest (ROIs) is associated with correlated tau-PET accumulation in corresponding ROIs. Third, we show that a model including baseline connectivity and tau-PET is associated with future tau-PET accumulation. Together, connectivity is associated with tau spread in AD, supporting the view of transneuronal tau propagation.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

Details

Title
Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease
Author
Franzmeier Nicolai 1   VIAFID ORCID Logo  ; Neitzel, Julia 1 ; Rubinski Anna 1 ; Smith, Ruben 2   VIAFID ORCID Logo  ; Strandberg Olof 3 ; Ossenkoppele Rik 4 ; Hansson Oskar 5   VIAFID ORCID Logo  ; Ewers, Michael 1 ; Weiner, Michael 6 ; Aisen, Paul 7 ; Petersen, Ronald 8 ; Jack, Clifford R, Jr 8 ; Jagust, William 9 ; Trojanowki, John Q 10 ; Toga, Arthur W 11 ; Beckett, Laurel 12 ; Green, Robert C 13 ; Saykin, Andrew J 14 ; Morris, John 15 ; Shaw, Leslie M 16 ; Liu Enchi 17 ; Montine, Tom 18 ; Thomas, Ronald G 7 ; Donohue, Michael 7 ; Walter, Sarah 7 ; Gessert Devon 7 ; Sather Tamie 7 ; Jiminez Gus 7 ; Harvey, Danielle 12 ; Bernstein, Matthew 8 ; Fox, Nick 19 ; Thompson, Paul 20 ; Schuff Norbert 21 ; DeCArli, Charles 12 ; Borowski Bret 8 ; Gunter, Jeff 8 ; Senjem Matt 8 ; Vemuri Prashanthi 8 ; Jones, David 8 ; Kantarci Kejal 8 ; Ward, Chad 8 ; Koeppe, Robert A 22 ; Foster, Norm 23 ; Reiman, Eric M 24 ; Chen, Kewei 24 ; Mathis, Chet 25 ; Landau, Susan 9 ; Cairns, Nigel J 15 ; Householder, Erin 15 ; Reinwald Lisa Taylor 15 ; Lee, Virginia 26 ; Korecka Magdalena 26 ; Figurski Michal 26 ; Crawford, Karen 11 ; Neu, Scott 11 ; Foroud, Tatiana M 14 ; Potkin, Steven 27 ; Shen, Li 14 ; Faber, Kelley 14 ; Kim, Sungeun 14 ; Nho Kwangsik 14 ; Kachaturian Zaven 28 ; Frank, Richard 29 ; Snyder, Peter J 30 ; Molchan, Susan 31 ; Kaye, Jeffrey 32 ; Quinn, Joseph 32 ; Lind, Betty 32 ; Carter, Raina 32 ; Dolen, Sara 32 ; Schneider, Lon S 33 ; Pawluczyk Sonia 33 ; Beccera Mauricio 33 ; Liberty, Teodoro 33 ; Spann, Bryan M 33 ; Brewer, James 34 ; Vanderswag Helen 34 ; Fleisher, Adam 34 ; Heidebrink, Judith L 22 ; Lord, Joanne L 22 ; Mason, Sara S 8 ; Albers, Colleen S 8 ; Knopman, David 8 ; Johnson, Kris 8 ; Doody, Rachelle S 35 ; Meyer Javier Villanueva 35 ; Chowdhury Munir 35 ; Rountree, Susan 35 ; Dang, Mimi 35 ; Stern, Yaakov 36 ; Honig, Lawrence S 36 ; Bell, Karen L 36 ; Ances Beau 37 ; Morris, John C 37 ; Carroll, Maria 37 ; Leon, Sue 37 ; Mintun Mark A 37 ; Schneider, Stacy 37 ; OliverNG Angela 38 ; Griffith, Randall 38 ; Clark, David 38 ; Geldmacher, David 38 ; Brockington, John 38 ; Roberson, Erik 38 ; Grossman, Hillel 39 ; Mitsis Effie 39 ; deToledo-Morrell Leyla 40 ; Shah, Raj C 40 ; Duara Ranjan 41 ; Varon, Daniel 41 ; Greig, Maria T 41 ; Roberts, Peggy 41 ; Albert, Marilyn 42 ; Onyike Chiadi 42 ; D’Agostino Daniel II 42 ; Kielb, Stephanie 42 ; Galvin, James E 43 ; Pogorelec, Dana M 43 ; Cerbone Brittany 43 ; Michel, Christina A 43 ; Rusinek, Henry 43 ; de Leon Mony J 43 ; Glodzik Lidia 43 ; De, Santi Susan 43 ; Murali, Doraiswamy P 44 ; Petrella, Jeffrey R 44 ; Wong, Terence Z 44 ; Arnold, Steven E 16 ; Karlawish, Jason H 16 ; Wolk, David 16 ; Smith, Charles D 45 ; Jicha, Greg 45 ; Hardy, Peter 45 ; Sinha Partha 45 ; Oates, Elizabeth 45 ; Conrad, Gary 45 ; Lopez, Oscar L 25 ; Oakley, MaryAnn 25 ; Simpson, Donna M 25 ; Porsteinsson, Anton P 46 ; Goldstein, Bonnie S 46 ; Kim, Martin 46 ; Makino, Kelly M 46 ; Saleem, Ismail M 46 ; Brand, Connie 46 ; Mulnard, Ruth A 47 ; Thai Gaby 47 ; Mc Adams, Ortiz Catherine 47 ; Womack, Kyle 48 ; Mathews, Dana 48 ; Quiceno, Mary 48 ; Arrastia Ramon Diaz 48 ; King, Richard 48 ; Weiner, Myron 48 ; Cook, Kristen Martin 48 ; DeVous, Michael 48 ; Levey, Allan I 49 ; Lah, James J 49 ; Cellar, Janet S 49 ; Burns, Jeffrey M 50 ; Anderson, Heather S 50 ; Swerdlow, Russell H 50 ; Apostolova Liana 51 ; Tingus Kathleen 51 ; Woo, Ellen 51 ; Silverman, Daniel H, S 51 ; Lu, Po H 51 ; Bartzokis, George 51 ; Radford Neill R Graff 52 ; ParfittH Francine 52 ; Kendall, Tracy 52 ; Johnson, Heather 52 ; Farlow, Martin R 14 ; Hake, Ann Marie 14 ; Matthews, Brandy R 14 ; Herring, Scott 14 ; Hunt, Cynthia 14 ; van Dyck Christopher H 53 ; Carson, Richard E 53 ; MacAvoy, Martha G 53 ; Chertkow Howard 54 ; Bergman, Howard 54 ; Hosein, Chris 54 ; Black, Sandra 55 ; Stefanovic Bojana 55 ; Caldwell, Curtis 55 ; Hsiung Ging Yuek Robin 56 ; Feldman, Howard 56 ; Mudge Benita 56 ; Past Michele Assaly 56 ; Kertesz, Andrew 57 ; Rogers, John 57 ; Trost, Dick 57 ; Bernick, Charles 58 ; Munic Donna 58 ; Kerwin, Diana 59 ; Mesulam Marek Marsel 59 ; Lipowski Kristine 59 ; Wu Chuang Kuo 59 ; Johnson, Nancy 59 ; Sadowsky, Carl 60 ; Martinez, Walter 60 ; Villena, Teresa 60 ; Turner, Raymond Scott 61 ; Johnson, Kathleen 61 ; Reynolds, Brigid 61 ; Sperling, Reisa A 62 ; Johnson, Keith A 62 ; Marshall, Gad 62 ; Frey, Meghan 62 ; Yesavage Jerome 63 ; Taylor, Joy L 63 ; Lane, Barton 63 ; Rosen, Allyson 63 ; Tinklenberg Jared 63 ; Sabbagh, Marwan N 64 ; Belden, Christine M 64 ; Jacobson, Sandra A 64 ; Sirrel, Sherye A 64 ; Kowall, Neil 65 ; Killiany, Ronald 65 ; Budson, Andrew E 65 ; Norbash, Alexander 65 ; Johnson, Patricia Lynn 65 ; Obisesan, Thomas O 66 ; Wolday Saba 66 ; Allard, Joanne 66 ; Lerner, Alan 67 ; Ogrocki Paula 67 ; Hudson, Leon 67 ; Fletcher, Evan 68 ; Carmichael, Owen 68 ; Olichney, John 68 ; DeCarli, Charles 68 ; Kittur Smita 69 ; Borrie, Michael 70 ; Lee, T Y 70 ; Bartha, Rob 70 ; Johnson, Sterling 71 ; Asthana Sanjay 71 ; Carlsson, Cynthia M 71 ; Potkin, Steven G 72 ; Preda, Adrian 72 ; Nguyen, Dana 72 ; Tariot Pierre 24 ; Reeder, Stephanie 24 ; Bates Vernice 73 ; Capote Horacio 73 ; Rainka Michelle 73 ; Scharre, Douglas W 74 ; Kataki, Maria 74 ; Adeli Anahita 74 ; Zimmerman, Earl A 75 ; Celmins Dzintra 75 ; Brown, Alice D 75 ; Pearlson, Godfrey D 76 ; Blank, Karen 76 ; Anderson, Karen 76 ; Santulli, Robert B 77 ; Kitzmiller, Tamar J 77 ; Schwartz, Eben S 77 ; SinkS, Kaycee M 78 ; Williamson, Jeff D 78 ; Garg Pradeep 78 ; Watkins, Franklin 78 ; Ott, Brian R 79 ; Querfurth, Henry 79 ; Tremont, Geoffrey 79 ; Salloway, Stephen 80 ; Malloy, Paul 80 ; Correia, Stephen 80 ; Rosen, Howard J 6 ; Miller, Bruce L 6 ; Mintzer Jacobo 81 ; Spicer, Kenneth 81 ; Bachman, David 81 ; Finger Elizabether 82 ; Pasternak, Stephen 82 ; Rachinsky Irina 82 ; Drost, Dick 82 ; Pomara Nunzio 83 ; Hernando Raymundo 83 ; Sarrael Antero 83 ; Schultz, Susan K 84 ; Ponto Laura L Boles 84 ; Shim Hyungsub 84 ; Smith, Karen Elizabeth 84 ; Relkin, Norman 85 ; Chaing Gloria 85 ; Raudin Lisa 85 ; Smith, Amanda 86 ; Fargher, Kristin 86 ; Ashok, Raj Balebail 86 

1  Ludwig-Maximilians-Universitat LMU, Institute for Stroke and Dementia Research, Klinikum der Universitat München, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X) 
2  Skane University Hospital, Department of Neurology, Lund, Sweden (GRID:grid.411843.b) (ISNI:0000 0004 0623 9987); Lund University, Clinical Memory Research Unit, Department of Clinical Sciences Malmo, Lund, Sweden (GRID:grid.4514.4) (ISNI:0000 0001 0930 2361) 
3  Lund University, Clinical Memory Research Unit, Department of Clinical Sciences Malmo, Lund, Sweden (GRID:grid.4514.4) (ISNI:0000 0001 0930 2361) 
4  Lund University, Clinical Memory Research Unit, Department of Clinical Sciences Malmo, Lund, Sweden (GRID:grid.4514.4) (ISNI:0000 0001 0930 2361); Vrije Universiteit Amsterdam, Amsterdam UMC, Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, the Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
5  Lund University, Clinical Memory Research Unit, Department of Clinical Sciences Malmo, Lund, Sweden (GRID:grid.4514.4) (ISNI:0000 0001 0930 2361); Skane University Hospital, Memory Clinic, Malmo, Sweden (GRID:grid.411843.b) (ISNI:0000 0004 0623 9987) 
6  UC San Francisco, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
7  UC San Diego, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242) 
8  Mayo Clinic, Rochester, USA (GRID:grid.66875.3a) (ISNI:0000 0004 0459 167X) 
9  UC Berkeley, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878) 
10  U Pennsylvania, Pennsylvania, USA (GRID:grid.47840.3f) 
11  USC, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
12  UC Davis, Davis, USA (GRID:grid.27860.3b) (ISNI:0000 0004 1936 9684) 
13  Harvard Medical School, Brigham and Women’s Hospital, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
14  Indiana University, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X) 
15  Washington University St. Louis, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
16  University of Pennsylvania, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
17  Janssen Alzheimer Immunotherapy, South San Francisco, USA (GRID:grid.25879.31) 
18  University of Washington, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
19  University of London, London, UK (GRID:grid.4464.2) (ISNI:0000 0001 2161 2573) 
20  USC School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
21  UCSF MRI, San Francisco, USA (GRID:grid.42505.36) 
22  University of Michigan, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
23  University of Utah, Salt Lake City, USA (GRID:grid.223827.e) (ISNI:0000 0001 2193 0096) 
24  Banner Alzheimer’s Institute, Phoenix, USA (GRID:grid.418204.b) (ISNI:0000 0004 0406 4925) 
25  University of Pittsburgh, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000) 
26  UPenn School of Medicine, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
27  UC Irvine, Newport Beach, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
28  Inc and Alzheimer’s Association’s Ronald and Nancy Reagan’s Research Institute, Khachaturian, Radebaugh & Associates, Chicago, USA (GRID:grid.411377.7) 
29  General Electric, Boston, USA (GRID:grid.418143.b) (ISNI:0000 0001 0943 0267) 
30  Brown University, Providence, USA (GRID:grid.40263.33) (ISNI:0000 0004 1936 9094) 
31  National Institute on Aging/National Institutes of Health, Bethesda, USA (GRID:grid.419475.a) (ISNI:0000 0000 9372 4913) 
32  Oregon Health and Science University, Portland, USA (GRID:grid.5288.7) (ISNI:0000 0000 9758 5690) 
33  University of Southern California, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
34  University of California San Diego, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242) 
35  Baylor College of Medicine, Houston, USA (GRID:grid.39382.33) (ISNI:0000 0001 2160 926X) 
36  Columbia University Medical Center, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675) 
37  Washington University, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
38  University of Alabama Birmingham, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000000106344187) 
39  Mount Sinai School of Medicine, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
40  Rush University Medical Center, Chicago, USA (GRID:grid.240684.c) (ISNI:0000 0001 0705 3621) 
41  Wien Center, Vienna, Austria (GRID:grid.240684.c) 
42  Johns Hopkins University, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
43  New York University, New York, USA (GRID:grid.137628.9) (ISNI:0000 0004 1936 8753) 
44  Duke University Medical Center, Durham, USA (GRID:grid.189509.c) (ISNI:0000000100241216) 
45  University of Kentucky, city of Lexington, USA (GRID:grid.266539.d) (ISNI:0000 0004 1936 8438) 
46  University of Rochester Medical Center, Rochester, USA (GRID:grid.412750.5) (ISNI:0000 0004 1936 9166) 
47  University of California, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
48  University of Texas Southwestern Medical School, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121) 
49  Emory University, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
50  University of Kansas, Medical Center, Lawrence, USA (GRID:grid.412016.0) (ISNI:0000 0001 2177 6375) 
51  University of California, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718) 
52  Mayo Clinic, Jacksonville, USA (GRID:grid.417467.7) (ISNI:0000 0004 0443 9942) 
53  Yale University School of Medicine, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
54  McGill Univ., Montreal Jewish General Hospital, Montreal, USA (GRID:grid.47100.32) 
55  Sunnybrook Health Sciences, Toronto, Canada (GRID:grid.413104.3) (ISNI:0000 0000 9743 1587) 
56  U.B.C. Clinic for AD & Related Disorders, British Columbia, Canada (GRID:grid.413104.3) 
57  Cognitive Neurology St. Joseph’s, Toronto, Canada (GRID:grid.413104.3) 
58  Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725) 
59  Northwestern University, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507) 
60  Premiere Research Inst Palm Beach Neurology, West Palm Beach, USA (GRID:grid.477769.c) 
61  Georgetown University Medical Center, Washington, USA (GRID:grid.411667.3) (ISNI:0000 0001 2186 0438) 
62  Brigham and Women’s Hospital, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
63  Stanford University, Santa Clara County, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
64  Banner Sun Health Research Institute, Sun City, USA (GRID:grid.414208.b) (ISNI:0000 0004 0619 8759) 
65  Boston University, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558) 
66  Howard University, Washington, USA (GRID:grid.257127.4) (ISNI:0000 0001 0547 4545) 
67  Case Western Reserve University, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847) 
68  University of California, Davis Sacramento, USA (GRID:grid.67105.35) 
69  Neurological Care of CNY, New York, USA (GRID:grid.67105.35) 
70  Parkwood Hospital, Parkwood, USA (GRID:grid.67105.35) 
71  University of Wisconsin, Madison, USA (GRID:grid.28803.31) (ISNI:0000 0001 0701 8607) 
72  University of California, Irvine BIC, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
73  Dent Neurologic Institute, Amherst, USA (GRID:grid.417854.b) 
74  Ohio State University, Columbus, USA (GRID:grid.261331.4) (ISNI:0000 0001 2285 7943) 
75  Albany Medical College, Albany, USA (GRID:grid.413558.e) (ISNI:0000 0001 0427 8745) 
76  Hartford Hosp, Olin Neuropsychiatry Research Center, Hartford, USA (GRID:grid.277313.3) (ISNI:0000 0001 0626 2712) 
77  Dartmouth Hitchcock Medical Center, Albany, USA (GRID:grid.413480.a) (ISNI:0000 0004 0440 749X) 
78  Wake Forest University Health Sciences, Winston-Salem, USA (GRID:grid.412860.9) (ISNI:0000 0004 0459 1231) 
79  Rhode Island Hospital, Rhode Island, USA (GRID:grid.240588.3) (ISNI:0000 0001 0557 9478) 
80  Butler Hospital, Providence, USA (GRID:grid.273271.2) (ISNI:0000 0000 8593 9332) 
81  Medical University South Carolina, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475) 
82  St. Joseph’s Health Care, Toronto, Canada (GRID:grid.259828.c) 
83  Nathan Kline Institute, Orangeburg, USA (GRID:grid.250263.0) (ISNI:0000 0001 2189 4777) 
84  University of Iowa College of Medicine, Iowa City, USA (GRID:grid.214572.7) (ISNI:0000 0004 1936 8294) 
85  Cornell University, Ithaca, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
86  University of South Floriday: USF Health Byrd Alzheimer’s Institute, Tampa, USA (GRID:grid.488684.e) (ISNI:0000 0004 6085 581X) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-14159-1
ProQuest document ID
2343281349
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.