Cortical tau deposition follows patterns of entorhinal functional connectivity in aging

Adams, Jenna N.; Maass, Anne; Harrison, Theresa M.; Baker, Suzanne L.; Jagust, William J.

doi:10.7554/eLife.49132

Cortical tau deposition follows patterns of entorhinal functional connectivity in aging

Journal Article · Mon Sep 02 04:00:00 EDT 2019 · eLife

DOI:https://doi.org/10.7554/eLife.49132· OSTI ID:1572050

^[1]; Maass, Anne ^[2]; ^[1]; ^[3]; ^[4]

Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; German Center for Neurodegenerative Disease, Magdeburg (Germany)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Tau pathology first appears in the transentorhinal and anterolateral entorhinal cortex (alEC) in the aging brain. The transition to Alzheimer’s disease (AD) is hypothesized to involve amyloid-β (Aβ) facilitated tau spread through neural connections. We contrasted functional connectivity (FC) of alEC and posteromedial EC (pmEC), subregions of EC that differ in functional specialization and cortical connectivity, with the hypothesis that alEC-connected cortex would show greater tau deposition than pmEC-connected cortex. We used resting state fMRI to measure FC, and PET to measure tau and Aβ in cognitively normal older adults. Tau preferentially deposited in alEC-connected cortex compared to pmEC-connected or non-connected cortex, and stronger connectivity was associated with increased tau deposition. FC-tau relationships were present regardless of Aβ, although strengthened with Aβ. These results provide an explanation for the anatomic specificity of neocortical tau deposition in the aging brain and reveal relationships between normal aging and the evolution of AD.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Helmholtz-Gemeinschaft; Tau Consortium

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1572050

Journal Information:: eLife, Journal Name: eLife Vol. 8; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

References (71)

Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue: Validation of PET Tracer Marquié, Marta; Normandin, Marc D.; Vanderburg, Charles R. Annals of Neurology, Vol. 78, Issue 5 https://doi.org/10.1002/ana.24517	journal	September 2015
In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum: Tau and Amyloid in AD Cho, Hanna; Choi, Jae Yong; Hwang, Mi Song Annals of Neurology, Vol. 80, Issue 2 https://doi.org/10.1002/ana.24711	journal	July 2016
Longitudinal tau accumulation and atrophy in aging and alzheimer disease: Tau-PET and Atrophy Harrison, Theresa M.; La Joie, Renaud; Maass, Anne Annals of Neurology, Vol. 85, Issue 2 https://doi.org/10.1002/ana.25406	journal	January 2019
Functional neuroanatomy of the parahippocampal region: The lateral and medial entorhinal areas Kerr, Kristin M.; Agster, Kara L.; Furtak, Sharon C. Hippocampus, Vol. 17, Issue 9 https://doi.org/10.1002/hipo.20315	journal	January 2007
Neuropathological stageing of Alzheimer-related changes Braak, H.; Braak, E. Acta Neuropathologica, Vol. 82, Issue 4 https://doi.org/10.1007/BF00308809	journal	September 1991
On areas of transition between entorhinal allocortex and temporal isocortex in the human brain. Normal morphology and lamina-specific pathology in Alzheimer's disease Braak, H.; Braak, E. Acta Neuropathologica, Vol. 68, Issue 4 https://doi.org/10.1007/BF00690836	journal	January 1985
Tau seeding activity begins in the transentorhinal/entorhinal regions and anticipates phospho-tau pathology in Alzheimer’s disease and PART Kaufman, Sarah K.; Del Tredici, Kelly; Thomas, Talitha L. Acta Neuropathologica, Vol. 136, Issue 1 https://doi.org/10.1007/s00401-018-1855-6	journal	May 2018
A comprehensive data-driven analysis framework for detecting impairments in brain function networks with resting state fMRI in HIV-infected individuals on cART Anteraper, Sheeba Arnold; Gopinath, Kaundinya; Hoch, Michael J. Journal of NeuroVirology, Vol. 27, Issue 2 https://doi.org/10.1007/s13365-021-00943-7	journal	March 2021
Some connections of the entorhinal (area 28) and perirhinal (area 35) cortices of the rhesus monkey. II. Frontal lobe afferents Van Hoesen, Gary W.; Pandya, Deepak N.; Butters, Nelson Brain Research, Vol. 95, Issue 1 https://doi.org/10.1016/0006-8993(75)90205-X	journal	September 1975
The parahippocampal gyrus: New observations regarding its cortical connections in the monkey Van Hoesen, Gary W. Trends in Neurosciences, Vol. 5 https://doi.org/10.1016/0166-2236(82)90201-6	journal	January 1982
Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region Witter, M. P.; Groenewegen, H. J.; Lopes da Silva, F. H. Progress in Neurobiology, Vol. 33, Issue 3 https://doi.org/10.1016/0301-0082(89)90009-9	journal	January 1989
Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories Braak, H.; Braak, E. Neurobiology of Aging, Vol. 18, Issue 4 https://doi.org/10.1016/S0197-4580(97)00056-0	journal	July 1997
Graphical analysis of PET data applied to reversible and irreversible tracers Logan, Jean Nuclear Medicine and Biology, Vol. 27, Issue 7 https://doi.org/10.1016/S0969-8051(00)00137-2	journal	October 2000
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade Jack, Clifford R.; Knopman, David S.; Jagust, William J. The Lancet Neurology, Vol. 9, Issue 1 https://doi.org/10.1016/S1474-4422(09)70299-6	journal	January 2010
Tau-PET uptake: Regional variation in average SUVR and impact of amyloid deposition Vemuri, Prashanthi; Lowe, Val J.; Knopman, David S. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol. 6 https://doi.org/10.1016/j.dadm.2016.12.010	journal	January 2017
Considerations and code for partial volume correcting [ 18 F]-AV-1451 tau PET data Baker, Suzanne L.; Maass, Anne; Jagust, William J. Data in Brief, Vol. 15 https://doi.org/10.1016/j.dib.2017.10.024	journal	December 2017
Ultra-fast MRI of the human brain with simultaneous multi-slice imaging Feinberg, David A.; Setsompop, Kawin Journal of Magnetic Resonance, Vol. 229 https://doi.org/10.1016/j.jmr.2013.02.002	journal	April 2013
Biomarkers for tau pathology Schöll, Michael; Maass, Anne; Mattsson, Niklas Molecular and Cellular Neuroscience, Vol. 97 https://doi.org/10.1016/j.mcn.2018.12.001	journal	June 2019
Modelling large motion events in fMRI studies of patients with epilepsy Lemieux, Louis; Salek-Haddadi, Afraim; Lund, Torben E. Magnetic Resonance Imaging, Vol. 25, Issue 6 https://doi.org/10.1016/j.mri.2007.03.009	journal	July 2007
Anatomic localization of the transentorhinal region of the perirhinal cortex Taylor, Kirsten I.; Probst, Alphonse Neurobiology of Aging, Vol. 29, Issue 10 https://doi.org/10.1016/j.neurobiolaging.2007.03.024	journal	October 2008
Human anterolateral entorhinal cortex volumes are associated with cognitive decline in aging prior to clinical diagnosis Olsen, Rosanna K.; Yeung, Lok-Kin; Noly-Gandon, Alix Neurobiology of Aging, Vol. 57 https://doi.org/10.1016/j.neurobiolaging.2017.04.025	journal	September 2017
Age-related functional changes in domain-specific medial temporal lobe pathways Berron, David; Neumann, Katja; Maass, Anne Neurobiology of Aging, Vol. 65 https://doi.org/10.1016/j.neurobiolaging.2017.12.030	journal	May 2018
An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest Desikan, Rahul S.; Ségonne, Florent; Fischl, Bruce NeuroImage, Vol. 31, Issue 3 https://doi.org/10.1016/j.neuroimage.2006.01.021	journal	July 2006
A component based noise correction method (CompCor) for BOLD and perfusion based fMRI Behzadi, Yashar; Restom, Khaled; Liau, Joy NeuroImage, Vol. 37, Issue 1 https://doi.org/10.1016/j.neuroimage.2007.04.042	journal	August 2007
Not quite PIB-positive, not quite PIB-negative: Slight PIB elevations in elderly normal control subjects are biologically relevant Mormino, Elizabeth C.; Brandel, Michael G.; Madison, Cindee M. NeuroImage, Vol. 59, Issue 2 https://doi.org/10.1016/j.neuroimage.2011.07.098	journal	January 2012
Recent progress and outstanding issues in motion correction in resting state fMRI Power, Jonathan D.; Schlaggar, Bradley L.; Petersen, Steven E. NeuroImage, Vol. 105 https://doi.org/10.1016/j.neuroimage.2014.10.044	journal	January 2015
Evaluation of 2D multiband EPI imaging for high-resolution, whole-brain, task-based fMRI studies at 3T: Sensitivity and slice leakage artifacts Todd, Nick; Moeller, Steen; Auerbach, Edward J. NeuroImage, Vol. 124 https://doi.org/10.1016/j.neuroimage.2015.08.056	journal	January 2016
Amyloid and tau PET demonstrate region-specific associations in normal older people Lockhart, Samuel N.; Schöll, Michael; Baker, Suzanne L. NeuroImage, Vol. 150 https://doi.org/10.1016/j.neuroimage.2017.02.051	journal	April 2017
Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease Maass, Anne; Landau, Susan; Baker, Suzanne L. NeuroImage, Vol. 157 https://doi.org/10.1016/j.neuroimage.2017.05.058	journal	August 2017
Propagation of Tau Pathology in a Model of Early Alzheimer's Disease de Calignon, Alix; Polydoro, Manuela; Suárez-Calvet, Marc Neuron, Vol. 73, Issue 4 https://doi.org/10.1016/j.neuron.2011.11.033	journal	February 2012
Propagation of Tau Pathology in a Model of Early Alzheimer’s Disease de Calignon, Alix; Polydoro, Manuela; Suárez-Calvet, Marc Neuron, Vol. 76, Issue 2 https://doi.org/10.1016/j.neuron.2012.10.005	journal	October 2012
PET Imaging of Tau Deposition in the Aging Human Brain Schöll, Michael; Lockhart, Samuel N.; Schonhaut, Daniel R. Neuron, Vol. 89, Issue 5 https://doi.org/10.1016/j.neuron.2016.01.028	journal	March 2016
Functional Imbalance of Anterolateral Entorhinal Cortex and Hippocampal Dentate/CA3 Underlies Age-Related Object Pattern Separation Deficits Reagh, Zachariah M.; Noche, Jessica A.; Tustison, Nicholas J. Neuron, Vol. 97, Issue 5 https://doi.org/10.1016/j.neuron.2018.01.039	journal	March 2018
Synthesis and Evaluation of ¹¹ C-Labeled 6-Substituted 2-Arylbenzothiazoles as Amyloid Imaging Agents Mathis, Chester A.; Wang, Yanming; Holt, Daniel P. Journal of Medicinal Chemistry, Vol. 46, Issue 13 https://doi.org/10.1021/jm030026b	journal	June 2003
Physiological release of endogenous tau is stimulated by neuronal activity Pooler, Amy M.; Phillips, Emma C.; Lau, Dawn H. W. EMBO reports, Vol. 14, Issue 4 https://doi.org/10.1038/embor.2013.15	journal	February 2013
Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease Khan, Usman A.; Liu, Li; Provenzano, Frank A. Nature Neuroscience, Vol. 17, Issue 2 https://doi.org/10.1038/nn.3606	journal	December 2013
Neuronal activity enhances tau propagation and tau pathology in vivo Wu, Jessica W.; Hussaini, S. Abid; Bastille, Isle M. Nature Neuroscience, Vol. 19, Issue 8 https://doi.org/10.1038/nn.4328	journal	June 2016
Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging Fox, Michael D.; Raichle, Marcus E. Nature Reviews Neuroscience, Vol. 8, Issue 9 https://doi.org/10.1038/nrn2201	journal	September 2007
Two cortical systems for memory-guided behaviour Ranganath, Charan; Ritchey, Maureen Nature Reviews Neuroscience, Vol. 13, Issue 10 https://doi.org/10.1038/nrn3338	journal	September 2012
Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity Palmqvist, Sebastian; Schöll, Michael; Strandberg, Olof Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-01150-x	journal	October 2017
Imaging the evolution and pathophysiology of Alzheimer disease Jagust, William Nature Reviews Neuroscience, Vol. 19, Issue 11 https://doi.org/10.1038/s41583-018-0067-3	journal	September 2018
Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals Jacobs, Heidi I. L.; Hedden, Trey; Schultz, Aaron P. Nature Neuroscience, Vol. 21, Issue 3 https://doi.org/10.1038/s41593-018-0070-z	journal	February 2018
Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo Busche, Marc Aurel; Wegmann, Susanne; Dujardin, Simon Nature Neuroscience, Vol. 22, Issue 1 https://doi.org/10.1038/s41593-018-0289-8	journal	December 2018
Kinetic Modeling of Amyloid Binding in Humans using PET Imaging and Pittsburgh Compound-B Price, Julie C.; Klunk, William E.; Lopresti, Brian J. Journal of Cerebral Blood Flow & Metabolism, Vol. 25, Issue 11 https://doi.org/10.1038/sj.jcbfm.9600146	journal	May 2005
Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease Salloway, Stephen; Sperling, Reisa; Fox, Nick C. New England Journal of Medicine, Vol. 370, Issue 4 https://doi.org/10.1056/NEJMoa1304839	journal	January 2014
Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer’s Disease Egan, Michael F.; Kost, James; Tariot, Pierre N. New England Journal of Medicine, Vol. 378, Issue 18 https://doi.org/10.1056/NEJMoa1706441	journal	May 2018
Object and spatial mnemonic interference differentially engage lateral and medial entorhinal cortex in humans Reagh, Zachariah M.; Yassa, Michael A. Proceedings of the National Academy of Sciences, Vol. 111, Issue 40 https://doi.org/10.1073/pnas.1411250111	journal	September 2014
Architecture of the cerebral cortical association connectome underlying cognition Bota, Mihail; Sporns, Olaf; Swanson, Larry W. Proceedings of the National Academy of Sciences, Vol. 112, Issue 16 https://doi.org/10.1073/pnas.1504394112	journal	April 2015
Neuronal activity regulates extracellular tau in vivo Yamada, Kaoru; Holth, Jerrah K.; Liao, Fan The Journal of Experimental Medicine, Vol. 211, Issue 3 https://doi.org/10.1084/jem.20131685	journal	February 2014
Neuronal activity regulates extracellular tau in vivo Yamada, Kaoru; Holth, Jerrah K.; Liao, Fan The Journal of General Physiology, Vol. 143, Issue 4 https://doi.org/10.1085/jgp.1434oia12	journal	March 2014
Conn : A Functional Connectivity Toolbox for Correlated and Anticorrelated Brain Networks Whitfield-Gabrieli, Susan; Nieto-Castanon, Alfonso Brain Connectivity, Vol. 2, Issue 3 https://doi.org/10.1089/brain.2012.0073	journal	June 2012
Regional profiles of the candidate tau PET ligand ¹⁸ F-AV-1451 recapitulate key features of Braak histopathological stages Schwarz, Adam J.; Yu, Peng; Miller, Bradley B. Brain, Vol. 139, Issue 5 https://doi.org/10.1093/brain/aww023	journal	March 2016
Tau burden and the functional connectome in Alzheimer’s disease and progressive supranuclear palsy Cope, Thomas E.; Rittman, Timothy; Borchert, Robin J. Brain, Vol. 141, Issue 2 https://doi.org/10.1093/brain/awx347	journal	January 2018
Functional connectivity associated with tau levels in ageing, Alzheimer’s, and small vessel disease Franzmeier, Nicolai; Rubinski, Anna; Neitzel, Julia Brain, Vol. 142, Issue 4 https://doi.org/10.1093/brain/awz026	journal	February 2019
Alzheimer’s pathology targets distinct memory networks in the ageing brain Maass, Anne; Berron, David; Harrison, Theresa M. Brain, Vol. 142, Issue 8 https://doi.org/10.1093/brain/awz154	journal	June 2019
Distinct Cortical Anatomy Linked to Subregions of the Medial Temporal Lobe Revealed by Intrinsic Functional Connectivity Kahn, Itamar; Andrews-Hanna, Jessica R.; Vincent, Justin L. Journal of Neurophysiology, Vol. 100, Issue 1 https://doi.org/10.1152/jn.00077.2008	journal	July 2008
Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer’s disease Pooler, Amy M.; Polydoro, Manuela; Maury, Eduardo A. Acta Neuropathologica Communications, Vol. 3, Issue 1 https://doi.org/10.1186/s40478-015-0199-x	journal	March 2015
Phases of Aβ-deposition in the human brain and its relevance for the development of AD Thal, Dietmar R.; Rüb, Udo; Orantes, Mario Neurology, Vol. 58, Issue 12 https://doi.org/10.1212/WNL.58.12.1791	journal	June 2002
Anatomical evidence for direct projections from the entorhinal area to the entire cortical mantle in the rat Swanson, Lw; Kohler, C. The Journal of Neuroscience, Vol. 6, Issue 10 https://doi.org/10.1523/JNEUROSCI.06-10-03010.1986	journal	October 1986
In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain Sepulcre, J.; Schultz, A. P.; Sabuncu, M. Journal of Neuroscience, Vol. 36, Issue 28 https://doi.org/10.1523/JNEUROSCI.0639-16.2016	journal	July 2016
Phases of Hyperconnectivity and Hypoconnectivity in the Default Mode and Salience Networks Track with Amyloid and Tau in Clinically Normal Individuals Schultz, Aaron P.; Chhatwal, Jasmeer P.; Hedden, Trey The Journal of Neuroscience, Vol. 37, Issue 16 https://doi.org/10.1523/JNEUROSCI.3263-16.2017	journal	March 2017
Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults Huijbers, W.; Mormino, E. C.; Wigman, S. E. Journal of Neuroscience, Vol. 34, Issue 15 https://doi.org/10.1523/JNEUROSCI.3579-13.2014	journal	April 2014
Differential Connectivity of Perirhinal and Parahippocampal Cortices within Human Hippocampal Subregions Revealed by High-Resolution Functional Imaging Libby, L. A.; Ekstrom, A. D.; Ragland, J. D. Journal of Neuroscience, Vol. 32, Issue 19 https://doi.org/10.1523/JNEUROSCI.3711-11.2012	journal	May 2012
Direct Evidence for Domain-Sensitive Functional Subregions in Human Entorhinal Cortex Schultz, H.; Sommer, T.; Peters, J. Journal of Neuroscience, Vol. 32, Issue 14 https://doi.org/10.1523/JNEUROSCI.5126-11.2012	journal	April 2012
Tau Burden and the Functional Connectome in Alzheimer's Disease and Progressive Supranuclear Palsy Cope, Thomas; Rittman, Timothy; Borchert, R. Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.14319	text	January 2017
Functional Imbalance of Anterolateral Entorhinal Cortex and Hippocampal Dentate/CA3 Underlies Age-Related Object Pattern Separation Deficits Reagh, Zachariah M.; Noche, Jessica A.; Tustison, Nicholas J. SSRN Electronic Journal https://doi.org/10.2139/ssrn.3155768	journal	January 2018
Aβ Accelerates the Spatiotemporal Progression of Tau Pathology and Augments Tau Amyloidosis in an Alzheimer Mouse Model Hurtado, David E.; Molina-Porcel, Laura; Iba, Michiyo The American Journal of Pathology, Vol. 177, Issue 4 https://doi.org/10.2353/ajpath.2010.100346	journal	October 2010
Spatiotemporal Distribution of β-Amyloid in Alzheimer Disease Is the Result of Heterogeneous Regional Carrying Capacities Whittington, Alex; Sharp, David J.; Gunn, Roger N. Journal of Nuclear Medicine, Vol. 59, Issue 5 https://doi.org/10.2967/jnumed.117.194720	journal	November 2017
Ckmeans.1d.dp: Optimal k-means Clustering in One Dimension by Dynamic Programming Wang, Haizhou; Song, Mingzhou The R Journal, Vol. 3, Issue 2 https://doi.org/10.32614/RJ-2011-015	journal	January 2011
Functional subregions of the human entorhinal cortex Maass, Anne; Berron, David; Libby, Laura A. eLife, Vol. 4 https://doi.org/10.7554/eLife.06426	journal	June 2015
Functional topography of the human entorhinal cortex Navarro Schröder, Tobias; Haak, Koen V.; Zaragoza Jimenez, Nestor I. eLife, Vol. 4 https://doi.org/10.7554/eLife.06738	journal	June 2015

Cited By (1)

Tau deposition is associated with functional isolation of the hippocampus in aging Harrison, Theresa M.; Maass, Anne; Adams, Jenna N. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-12921-z	journal	October 2019

Similar Records

Regional Tau Effects on Prospective Cognitive Change in Cognitively Normal Older Adults

Journal Article · Thu Nov 19 23:00:00 EST 2020 · Journal of Neuroscience · OSTI ID:1827916

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

Journal Article · Wed Mar 22 00:00:00 EDT 2017 · Journal of Neuroscience · OSTI ID:1393136

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

Cortical tau deposition follows patterns of entorhinal functional connectivity in aging

Citation Formats

References (71)

Cited By (1)

Similar Records

Related Subjects