Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease

Iaccarino, Leonardo; Tammewar, Gautam; Ayakta, Nagehan; Baker, Suzanne L.; Bejanin, Alexandre; Boxer, Adam L.; Gorno-Tempini, Maria Luisa; Janabi, Mustafa; Kramer, Joel H.; Lazaris, Andreas; Lockhart, Samuel N.; Miller, Bruce L.; Miller, Zachary A.; O'Neil, James P.; Ossenkoppele, Rik; Rosen, Howard J.; Schonhaut, Daniel R.; Jagust, William J.; Rabinovici, Gil D.

doi:10.1016/j.nicl.2017.09.016

Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease

Journal Article · Sun Dec 31 23:00:00 EST 2017 · NeuroImage: Clinical

DOI:https://doi.org/10.1016/j.nicl.2017.09.016· OSTI ID:1623707

Iaccarino, Leonardo ^[1]; Tammewar, Gautam ^[2]; Ayakta, Nagehan ^[2]; Baker, Suzanne L. ^[3]; Bejanin, Alexandre ^[2]; Boxer, Adam L. ^[2]; Gorno-Tempini, Maria Luisa ^[2]; Janabi, Mustafa ^[4]; Kramer, Joel H. ^[2]; Lazaris, Andreas ^[5]; Lockhart, Samuel N. ^[6]; Miller, Bruce L. ^[2]; Miller, Zachary A. ^[2]; O'Neil, James P. ^[4]; Ossenkoppele, Rik ^[7]; Rosen, Howard J. ^[2]; Schonhaut, Daniel R. ^[5]; Jagust, William J. ^[3]; Rabinovici, Gil D. ^[8]

Univ. of California, San Francisco, CA (United States). Sandler Neurosciences Center. Memory and Aging Center; Vita-Salute San Raffaele Univ., Milan (Italy); IRCCS San Raffaele Scientific Inst., Milan (Italy). Division of Neuroscience. In Vivo Human Molecular and Structural Neuroimaging Unit; DOE/OSTI
Univ. of California, San Francisco, CA (United States). Sandler Neurosciences Center. Memory and Aging Center
Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
Univ. of California, San Francisco, CA (United States). Sandler Neurosciences Center. Memory and Aging Center; Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
Univ. of California, San Francisco, CA (United States). Sandler Neurosciences Center. Memory and Aging Center; Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; VU Univ. Medical Center, Amsterdam (The Netherlands). Dept. of Neurology and Alzheimer Center
Univ. of California, San Francisco, CA (United States). Sandler Neurosciences Center. Memory and Aging Center; Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division

The relationships between β-amyloid (Aβ), tau and neurodegeneration within Alzheimer's Disease pathogenesis are not fully understood. To explore these associations in vivo, we evaluated 30 Aβ PET-positive patients (mean ± sd age 62.4 ± 8.3) with mild probable AD and 12 Aβ PET-negative healthy controls (HC) (mean ± sd age 77.3 ± 6.9) as comparison. All participants underwent 3 T MRI, 11C-PiB (Aβ) PET and 18FAV1451 (tau) PET. Multimodal correlation analyses were run at both voxel- and region-of-interest levels. 11C-PiB retention in AD showed the most diffuse uptake pattern throughout association neocortex, whereas 18F-AV1451 and gray matter volume reduction (GMR) showed a progressive predilection for posterior cortices (p < 0.05 Family-Wise Error-[FWE]-corrected). Voxel-level analysis identified negative correlations between 18F-AV1451 and gray matter peaking in medial and infero-occipital regions (p < 0.01 False Discovery Rate-[FDR]-corrected). 18F-AV1451 and 11C-PiB were positively correlated in right parietal and medial/inferior occipital regions (p < 0.001 uncorrected). 11C-PiB did not correlate with GMR at the voxel-level. Regionally, 18F-AV1451 was largely associated with local/adjacent GMR whereas frontal 11C-PiB correlated with GMR in posterior regions. These findings suggest that, in mild AD, tau aggregation drives local neurodegeneration, whereas the relationships between Aβ and neurodegeneration are not region specific and may be mediated by the interaction between Aβ and tau.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1623707

Journal Information:: NeuroImage: Clinical, Journal Name: NeuroImage: Clinical Journal Issue: C Vol. 17; ISSN 2213-1582

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (103)

Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia: A Meta-analysis Jansen, Willemijn J.; Ossenkoppele, Rik; Knol, Dirk L. JAMA, Vol. 313, Issue 19 https://doi.org/10.1001/jama.2015.4668	journal	May 2015
Tau and Cortical Thickness in Alzheimer Disease Masdeu, Joseph C. JAMA Neurology, Vol. 74, Issue 4 https://doi.org/10.1001/jamaneurol.2016.5701	journal	April 2017
Impact of tau and amyloid burden on glucose metabolism in Alzheimer's disease Bischof, Gérard N.; Jessen, Frank; Fliessbach, Klaus Annals of Clinical and Translational Neurology, Vol. 3, Issue 12 https://doi.org/10.1002/acn3.339	journal	October 2016
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
Imaging in-vivo tau pathology in Alzheimer’s disease with THK5317 PET in a multimodal paradigm Chiotis, Konstantinos; Saint-Aubert, Laure; Savitcheva, Irina European Journal of Nuclear Medicine and Molecular Imaging, Vol. 43, Issue 9 https://doi.org/10.1007/s00259-016-3363-z	journal	March 2016
National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach Montine, Thomas J.; Phelps, Creighton H.; Beach, Thomas G. Acta Neuropathologica, Vol. 123, Issue 1 https://doi.org/10.1007/s00401-011-0910-3	journal	November 2011
Heterotypic seeding of Tau fibrillization by pre-aggregated Abeta provides potent seeds for prion-like seeding and propagation of Tau-pathology in vivo Vasconcelos, Bruno; Stancu, Ilie-Cosmin; Buist, Arjan Acta Neuropathologica, Vol. 131, Issue 4 https://doi.org/10.1007/s00401-015-1525-x	journal	January 2016
Advances in the development of tau PET radiotracers and their clinical applications Okamura, Nobuyuki; Harada, Ryuichi; Furukawa, Katsutoshi Ageing Research Reviews, Vol. 30 https://doi.org/10.1016/j.arr.2015.12.010	journal	September 2016
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
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease McKhann, Guy M.; Knopman, David S.; Chertkow, Howard Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.005	journal	May 2011
National Institute on Aging–Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease Hyman, Bradley T.; Phelps, Creighton H.; Beach, Thomas G. Alzheimer's & Dementia, Vol. 8, Issue 1 https://doi.org/10.1016/j.jalz.2011.10.007	journal	January 2012
Tau immunotherapy for Alzheimer's disease Pedersen, Jan Torleif; Sigurdsson, Einar M. Trends in Molecular Medicine, Vol. 21, Issue 6 https://doi.org/10.1016/j.molmed.2015.03.003	journal	June 2015
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
Biological parametric mapping: A statistical toolbox for multimodality brain image analysis Casanova, Ramon; Srikanth, Ryali; Baer, Aaron NeuroImage, Vol. 34, Issue 1 https://doi.org/10.1016/j.neuroimage.2006.09.011	journal	January 2007
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
Defining Neurocognitive Networks in the BOLD New World of Computed Connectivity Mesulam, Marsel Neuron, Vol. 62, Issue 1 https://doi.org/10.1016/j.neuron.2009.04.001	journal	April 2009
Predicting Regional Neurodegeneration from the Healthy Brain Functional Connectome Zhou, Juan; Gennatas, Efstathios D.; Kramer, Joel H. Neuron, Vol. 73, Issue 6 https://doi.org/10.1016/j.neuron.2012.03.004	journal	March 2012
Disintegrating Brain Networks: from Syndromes to Molecular Nexopathies Warren, Jason D.; Rohrer, Jonathan D.; Hardy, John Neuron, Vol. 73, Issue 6 https://doi.org/10.1016/j.neuron.2012.03.006	journal	March 2012
Anti-Tau Antibodies that Block Tau Aggregate Seeding In Vitro Markedly Decrease Pathology and Improve Cognition In Vivo Yanamandra, Kiran; Kfoury, Najla; Jiang, Hong Neuron, Vol. 80, Issue 2 https://doi.org/10.1016/j.neuron.2013.07.046	journal	October 2013
Biomarker Modeling of Alzheimer’s Disease Jack, Clifford R.; Holtzman, David M. Neuron, Vol. 80, Issue 6 https://doi.org/10.1016/j.neuron.2013.12.003	journal	December 2013
The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease Spires-Jones, Tara L.; Hyman, Bradley T. Neuron, Vol. 82, Issue 4 https://doi.org/10.1016/j.neuron.2014.05.004	journal	May 2014
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
Parallel ICA of FDG-PET and PiB-PET in three conditions with underlying Alzheimer's pathology Laforce, Robert; Tosun, Duygu; Ghosh, Pia NeuroImage: Clinical, Vol. 4 https://doi.org/10.1016/j.nicl.2014.03.005	journal	January 2014
Biomarkers for Alzheimer's: the sequel of an original model Frisoni, Giovanni B.; Blennow, Kaj The Lancet Neurology, Vol. 12, Issue 2 https://doi.org/10.1016/s1474-4422(12)70305-8	journal	February 2013
Tau imaging: early progress and future directions Villemagne, Victor L.; Fodero-Tavoletti, Michelle T.; Masters, Colin L. The Lancet Neurology, Vol. 14, Issue 1 https://doi.org/10.1016/s1474-4422(14)70252-2	journal	January 2015
Measurement of Radiotracer Concentration in Brain Gray Matter Using Positron Emission Tomography: MRI-Based Correction for Partial Volume Effects Müller-Gärtner, Hans W.; Links, Jonathan M.; Prince, Jerry L. Journal of Cerebral Blood Flow & Metabolism, Vol. 12, Issue 4 https://doi.org/10.1038/jcbfm.1992.81	journal	July 1992
Three dimensions of the amyloid hypothesis: time, space and 'wingmen' Musiek, Erik S.; Holtzman, David M. Nature Neuroscience, Vol. 18, Issue 6 https://doi.org/10.1038/nn.4018	journal	May 2015
Tau in physiology and pathology Wang, Yipeng; Mandelkow, Eckhard Nature Reviews Neuroscience, Vol. 17, Issue 1 https://doi.org/10.1038/nrn.2015.1	journal	December 2015
Amyloid-β and tau — a toxic pas de deux in Alzheimer's disease Ittner, Lars M.; Götz, Jürgen Nature Reviews Neuroscience, Vol. 12, Issue 2 https://doi.org/10.1038/nrn2967	journal	December 2010
The paradox of syndromic diversity in Alzheimer disease Warren, Jason D.; Fletcher, Phillip D.; Golden, Hannah L. Nature Reviews Neurology, Vol. 8, Issue 8 https://doi.org/10.1038/nrneurol.2012.135	journal	July 2012
Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition Vlassenko, Andrei G.; Vaishnavi, S. Neil; Couture, Lars Proceedings of the National Academy of Sciences, Vol. 107, Issue 41 https://doi.org/10.1073/pnas.1010461107	journal	September 2010
Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients Kim, E. J.; Cho, S. S.; Jeong, Y. Brain, Vol. 128, Issue 8 https://doi.org/10.1093/brain/awh539	journal	May 2005
Increased metabolic vulnerability in early-onset Alzheimer’s disease is not related to amyloid burden Rabinovici, Gil D.; Furst, Ansgar J.; Alkalay, Adi Brain, Vol. 133, Issue 2 https://doi.org/10.1093/brain/awp326	journal	January 2010
Amyloid burden and metabolic function in early-onset Alzheimer's disease: parietal lobe involvement Ossenkoppele, R.; Zwan, M. D.; Tolboom, N. Brain, Vol. 135, Issue 7 https://doi.org/10.1093/brain/aws113	journal	May 2012
Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer’s disease Lehmann, Manja; Ghosh, Pia M.; Madison, Cindee Brain, Vol. 136, Issue 3 https://doi.org/10.1093/brain/aws327	journal	January 2013
Clinicopathologic and ¹¹ C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer’s disease spectrum Murray, Melissa E.; Lowe, Val J.; Graff-Radford, Neill R. Brain, Vol. 138, Issue 5 https://doi.org/10.1093/brain/awv050	journal	March 2015
Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation Villeneuve, Sylvia; Rabinovici, Gil D.; Cohn-Sheehy, Brendan I. Brain, Vol. 138, Issue 7 https://doi.org/10.1093/brain/awv112	journal	May 2015
Regional brain hypometabolism is unrelated to regional amyloid plaque burden Altmann, Andre; Ng, Bernard; Landau, Susan M. Brain, Vol. 138, Issue 12 https://doi.org/10.1093/brain/awv278	journal	September 2015
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease Ossenkoppele, Rik; Schonhaut, Daniel R.; Schöll, Michael Brain, Vol. 139, Issue 5 https://doi.org/10.1093/brain/aww027	journal	March 2016
Distinct tau PET imaging patterns in typical and atypical Alzheimer’s disease Sarazin, Marie; Lagarde, Julien; Bottlaender, Michel Brain, Vol. 139, Issue 5 https://doi.org/10.1093/brain/aww041	journal	April 2016
Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition Pontecorvo, Michael J.; Devous, Michael D.; Navitsky, Michael Brain https://doi.org/10.1093/brain/aww334	journal	January 2017
Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data Logan, Jean; Fowler, Joanna S.; Volkow, Nora D. Journal of Cerebral Blood Flow & Metabolism, Vol. 16, Issue 5 https://doi.org/10.1097/00004647-199609000-00008	journal	September 1996
Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature Nelson, Peter T.; Alafuzoff, Irina; Bigio, Eileen H. Journal of Neuropathology & Experimental Neurology, Vol. 71, Issue 5 https://doi.org/10.1097/nen.0b013e31825018f7	journal	May 2012
Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease Brier, Matthew R.; Gordon, Brian; Friedrichsen, Karl Science Translational Medicine, Vol. 8, Issue 338 https://doi.org/10.1126/scitranslmed.aaf2362	journal	May 2016
Selective vulnerability in neurodegeneration: insights from clinical variants of Alzheimer's disease Mattsson, Niklas; Schott, Jonathan M.; Hardy, John Journal of Neurology, Neurosurgery & Psychiatry, Vol. 87, Issue 9 https://doi.org/10.1136/jnnp-2015-311321	journal	January 2016
Tau PET in Alzheimer disease and mild cognitive impairment Cho, Hanna; Choi, Jae Yong; Hwang, Mi Song Neurology, Vol. 87, Issue 4 https://doi.org/10.1212/wnl.0000000000002892	journal	June 2016
Regional rates of neocortical atrophy from normal aging to early Alzheimer disease McDonald, C. R.; McEvoy, L. K.; Gharapetian, L. Neurology, Vol. 73, Issue 6 https://doi.org/10.1212/wnl.0b013e3181b16431	journal	August 2009
-Amyloid burden in the temporal neocortex is related to hippocampal atrophy in elderly subjects without dementia Bourgeat, P.; Chetelat, G.; Villemagne, V. L. Neurology, Vol. 74, Issue 2 https://doi.org/10.1212/wnl.0b013e3181c918b5	journal	January 2010
Classification of primary progressive aphasia and its variants Gorno-Tempini, M. L.; Hillis, A. E.; Weintraub, S. Neurology, Vol. 76, Issue 11 https://doi.org/10.1212/wnl.0b013e31821103e6	journal	February 2011
Early-onset Alzheimer disease clinical variants: Multivariate analyses of cortical thickness Ridgway, G. R.; Lehmann, M.; Barnes, J. Neurology, Vol. 79, Issue 1 https://doi.org/10.1212/wnl.0b013e31825dce28	journal	June 2012
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
Region-Specific Hierarchy between Atrophy, Hypometabolism, and -Amyloid (A ) Load in Alzheimer's Disease Dementia La Joie, R.; Perrotin, A.; Barre, L. Journal of Neuroscience, Vol. 32, Issue 46 https://doi.org/10.1523/jneurosci.2170-12.2012	journal	November 2012
Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory Buckner, R. L. Journal of Neuroscience, Vol. 25, Issue 34 https://doi.org/10.1523/jneurosci.2177-05.2005	journal	August 2005
Basal Cerebral Metabolism May Modulate the Cognitive Effects of A in Mild Cognitive Impairment: An Example of Brain Reserve Cohen, A. D.; Price, J. C.; Weissfeld, L. A. Journal of Neuroscience, Vol. 29, Issue 47 https://doi.org/10.1523/jneurosci.3669-09.2009	journal	November 2009
Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease Buckner, R. L.; Sepulcre, J.; Talukdar, T. Journal of Neuroscience, Vol. 29, Issue 6 https://doi.org/10.1523/jneurosci.5062-08.2009	journal	February 2009
Induction of Tau Pathology by Intracerebral Infusion of Amyloid-β-Containing Brain Extract and by Amyloid-β Deposition in APP × Tau Transgenic Mice Bolmont, Tristan; Clavaguera, Florence; Meyer-Luehmann, Melanie The American Journal of Pathology, Vol. 171, Issue 6 https://doi.org/10.2353/ajpath.2007.070403	journal	December 2007
Prefrontal Hypometabolism in Alzheimer Disease Is Related to Longitudinal Amyloid Accumulation in Remote Brain Regions Klupp, E.; Grimmer, T.; Tahmasian, M. Journal of Nuclear Medicine, Vol. 56, Issue 3 https://doi.org/10.2967/jnumed.114.149302	journal	February 2015
In vivo Patterns of Tau Pathology, Amyloid-β Burden, and Neuronal Dysfunction in Clinical Variants of Alzheimer’s Disease Dronse, Julian; Fliessbach, Klaus; Bischof, Gérard N. Journal of Alzheimer's Disease, Vol. 55, Issue 2 https://doi.org/10.3233/jad-160316	journal	November 2016
ppcor: An R Package for a Fast Calculation to Semi-partial Correlation Coefficients Kim, Seongho Communications for Statistical Applications and Methods, Vol. 22, Issue 6 https://doi.org/10.5351/csam.2015.22.6.665	journal	November 2015
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria Bruno, Dubois,; H., Feldman, Howard; Claudia, Jacova, Columbia University https://doi.org/10.7916/dg3n-mf18	text	January 2014
Association of In Vivo [ ¹⁸ F]AV-1451 Tau PET Imaging Results With Cortical Atrophy and Symptoms in Typical and Atypical Alzheimer Disease Xia, Chenjie; Makaretz, Sara J.; Caso, Christina JAMA Neurology, Vol. 74, Issue 4 https://doi.org/10.1001/jamaneurol.2016.5755	journal	April 2017
Relationship between atrophy and Î²-amyloid deposition in Alzheimer's disease ChÃ©telat, GaÃ«l; Villemagne, Victor L.; Bourgeat, Pierrick Annals of Neurology https://doi.org/10.1002/ana.21955	journal	January 2009
Tau, amyloid, and hypometabolism in a patient with posterior cortical atrophy: Tau, Aβ, Hypometabolism in PCA Ossenkoppele, Rik; Schonhaut, Daniel R.; Baker, Suzanne L. Annals of Neurology, Vol. 77, Issue 2 https://doi.org/10.1002/ana.24321	journal	December 2014
Tau positron emission tomographic imaging in aging and early Alzheimer disease: Tau PET in Aging and Early AD Johnson, Keith A.; Schultz, Aaron; Betensky, Rebecca A. Annals of Neurology, Vol. 79, Issue 1 https://doi.org/10.1002/ana.24546	journal	December 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
Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease: Origin and Spread of Atrophy in AD Variants Ossenkoppele, Rik; Cohn-Sheehy, Brendan I.; La Joie, Renaud Human Brain Mapping, Vol. 36, Issue 11 https://doi.org/10.1002/hbm.22927	journal	August 2015
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
Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry Braak, Heiko; Alafuzoff, Irina; Arzberger, Thomas Acta Neuropathologica, Vol. 112, Issue 4 https://doi.org/10.1007/s00401-006-0127-z	journal	August 2006
PART is part of Alzheimer disease Duyckaerts, Charles; Braak, Heiko; Brion, Jean-Pierre Acta Neuropathologica, Vol. 129, Issue 5 https://doi.org/10.1007/s00401-015-1390-7	journal	January 2015
Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers Jack, Clifford R.; Knopman, David S.; Jagust, William J. The Lancet Neurology, Vol. 12, Issue 2 https://doi.org/10.1016/S1474-4422(12)70291-0	journal	February 2013
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria Dubois, Bruno; Feldman, Howard H.; Jacova, Claudia The Lancet Neurology, Vol. 13, Issue 6 https://doi.org/10.1016/S1474-4422(14)70090-0	journal	June 2014
Tau imaging: early progress and future directions Villemagne, Victor L.; Fodero-Tavoletti, Michelle T.; Masters, Colin L. The Lancet Neurology, Vol. 14, Issue 1 https://doi.org/10.1016/S1474-4422(14)70252-2	journal	January 2015
Biological parametric mapping with robust and non-parametric statistics Yang, Xue; Beason-Held, Lori; Resnick, Susan M. NeuroImage, Vol. 57, Issue 2 https://doi.org/10.1016/j.neuroimage.2011.04.046	journal	July 2011
Neurodegenerative Diseases Target Large-Scale Human Brain Networks Seeley, William W.; Crawford, Richard K.; Zhou, Juan Neuron, Vol. 62, Issue 1 https://doi.org/10.1016/j.neuron.2009.03.024	journal	April 2009
The Evolution of Preclinical Alzheimer’s Disease: Implications for Prevention Trials Sperling, Reisa; Mormino, Elizabeth; Johnson, Keith Neuron, Vol. 84, Issue 3 https://doi.org/10.1016/j.neuron.2014.10.038	journal	November 2014
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease Sevigny, Jeff; Chiao, Ping; Bussière, Thierry Nature, Vol. 537, Issue 7618 https://doi.org/10.1038/nature19323	journal	August 2016
The case for rejecting the amyloid cascade hypothesis Herrup, Karl Nature Neuroscience, Vol. 18, Issue 6 https://doi.org/10.1038/nn.4017	journal	May 2015
Spreading of pathology in neurodegenerative diseases: a focus on human studies Brettschneider, Johannes; Tredici, Kelly Del; Lee, Virginia M. -Y. Nature Reviews Neuroscience, Vol. 16, Issue 2 https://doi.org/10.1038/nrn3887	journal	January 2015
Deciphering the mechanism underlying late-onset Alzheimer disease Krstic, Dimitrije; Knuesel, Irene Nature Reviews Neurology, Vol. 9, Issue 1 https://doi.org/10.1038/nrneurol.2012.236	journal	November 2012
Aβ-independent processes—rethinking preclinical AD Chételat, Gaël Nature Reviews Neurology, Vol. 9, Issue 3 https://doi.org/10.1038/nrneurol.2013.21	journal	February 2013
Alzheimer disease therapy—moving from amyloid-β to tau Giacobini, Ezio; Gold, Gabriel Nature Reviews Neurology, Vol. 9, Issue 12 https://doi.org/10.1038/nrneurol.2013.223	journal	November 2013
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
Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease Doody, Rachelle S.; Thomas, Ronald G.; Farlow, Martin New England Journal of Medicine, Vol. 370, Issue 4 https://doi.org/10.1056/NEJMoa1312889	journal	January 2014
Alzheimer's Disease Querfurth, Henry W.; LaFerla, Frank M. New England Journal of Medicine, Vol. 362, Issue 4 https://doi.org/10.1056/NEJMra0909142	journal	January 2010
Is amyloid-β harmful to the brain? Insights from human imaging studies Jagust, William Brain, Vol. 139, Issue 1 https://doi.org/10.1093/brain/awv326	journal	November 2015
Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature Nelson, Peter T.; Alafuzoff, Irina; Bigio, Eileen H. Journal of Neuropathology & Experimental Neurology, Vol. 71, Issue 5 https://doi.org/10.1097/NEN.0b013e31825018f7	journal	May 2012
Alzheimer's disease: the amyloid cascade hypothesis Hardy, J.; Higgins, G. Science, Vol. 256, Issue 5054 https://doi.org/10.1126/science.1566067	journal	April 1992
Posterior Cortical Atrophy: Clinical Characteristics and Differences Compared to Alzheimer’s Disease Mendez, Mario F.; Ghajarania, Mehdi; Perryman, Kent M. Dementia and Geriatric Cognitive Disorders, Vol. 14, Issue 1 https://doi.org/10.1159/000058331	journal	January 2002
An autoradiographic evaluation of AV-1451 Tau PET in dementia Lowe, Val J.; Curran, Geoffry; Fang, Ping Acta Neuropathologica Communications, Vol. 4, Issue 1 https://doi.org/10.1186/s40478-016-0315-6	journal	June 2016
Association of hypometabolism and amyloid levels in aging, normal subjects Lowe, V. J.; Weigand, S. D.; Senjem, M. L. Neurology, Vol. 82, Issue 22 https://doi.org/10.1212/WNL.0000000000000467	journal	May 2014
Tau PET in Alzheimer disease and mild cognitive impairment Cho, Hanna; Choi, Jae Yong; Hwang, Mi Song Neurology, Vol. 87, Issue 4 https://doi.org/10.1212/WNL.0000000000002892	journal	June 2016
Regional rates of neocortical atrophy from normal aging to early Alzheimer disease McDonald, C. R.; McEvoy, L. K.; Gharapetian, L. Neurology, Vol. 73, Issue 6 https://doi.org/10.1212/WNL.0b013e3181b16431	journal	August 2009
-Amyloid burden in the temporal neocortex is related to hippocampal atrophy in elderly subjects without dementia Bourgeat, P.; Chetelat, G.; Villemagne, V. L. Neurology, Vol. 74, Issue 2 https://doi.org/10.1212/WNL.0b013e3181c918b5	journal	January 2010
Classification of primary progressive aphasia and its variants Gorno-Tempini, M. L.; Hillis, A. E.; Weintraub, S. Neurology, Vol. 76, Issue 11 https://doi.org/10.1212/WNL.0b013e31821103e6	journal	February 2011
Early-onset Alzheimer disease clinical variants: Multivariate analyses of cortical thickness Ridgway, G. R.; Lehmann, M.; Barnes, J. Neurology, Vol. 79, Issue 1 https://doi.org/10.1212/WNL.0b013e31825dce28	journal	June 2012
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
Region-Specific Hierarchy between Atrophy, Hypometabolism, and -Amyloid (A ) Load in Alzheimer's Disease Dementia La Joie, R.; Perrotin, A.; Barre, L. Journal of Neuroscience, Vol. 32, Issue 46 https://doi.org/10.1523/JNEUROSCI.2170-12.2012	journal	November 2012
Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory Buckner, R. L. Journal of Neuroscience, Vol. 25, Issue 34 https://doi.org/10.1523/JNEUROSCI.2177-05.2005	journal	August 2005
Basal Cerebral Metabolism May Modulate the Cognitive Effects of A in Mild Cognitive Impairment: An Example of Brain Reserve Cohen, A. D.; Price, J. C.; Weissfeld, L. A. Journal of Neuroscience, Vol. 29, Issue 47 https://doi.org/10.1523/JNEUROSCI.3669-09.2009	journal	November 2009
Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease Buckner, R. L.; Sepulcre, J.; Talukdar, T. Journal of Neuroscience, Vol. 29, Issue 6 https://doi.org/10.1523/JNEUROSCI.5062-08.2009	journal	February 2009
Reference Tissue–Based Kinetic Evaluation of ¹⁸ F-AV-1451 for Tau Imaging Baker, Suzanne L.; Lockhart, Samuel N.; Price, Julie C. Journal of Nuclear Medicine, Vol. 58, Issue 2 https://doi.org/10.2967/jnumed.116.175273	journal	September 2016
In vivo Patterns of Tau Pathology, Amyloid-β Burden, and Neuronal Dysfunction in Clinical Variants of Alzheimer’s Disease Dronse, Julian; Fliessbach, Klaus; Bischof, Gérard N. Journal of Alzheimer's Disease, Vol. 55, Issue 2 https://doi.org/10.3233/JAD-160316	journal	November 2016
An autoradiographic evaluation of AV-1451 Tau PET in dementia Lowe, Val; Curran, Geoffry; Fang, Ping Figshare https://doi.org/10.6084/m9.figshare.c.3645467	collection	January 2016

Cited By (28)

Could Alzheimer’s Disease Originate in the Periphery and If So How So? Morris, Gerwyn; Berk, Michael; Maes, Michael Molecular Neurobiology, Vol. 56, Issue 1 https://doi.org/10.1007/s12035-018-1092-y	journal	April 2018
Longitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease Sintini, Irene; Martin, Peter R.; Graff-Radford, Jonathan NeuroImage: Clinical, Vol. 23 https://doi.org/10.1016/j.nicl.2019.101823	journal	January 2019
Tau PET imaging in neurodegenerative tauopathies—still a challenge Leuzy, Antoine; Chiotis, Konstantinos; Lemoine, Laetitia Molecular Psychiatry, Vol. 24, Issue 8 https://doi.org/10.1038/s41380-018-0342-8	journal	January 2019
Tau pathology in cognitively normal older adults Ziontz, Jacob; Bilgel, Murat; Shafer, Andrea T. https://doi.org/10.1101/611186	posted_content	July 2019
Disrupted core-periphery structure of multimodal brain networks in Alzheimer’s disease Guillon, Jeremy; Chavez, Mario; Battiston, Federico Network Neuroscience, Vol. 3, Issue 2 https://doi.org/10.1162/netn_a_00087	journal	January 2019
Greater tau load and reduced cortical thickness in APOE ε4-negative Alzheimer’s disease: a cohort study Mattsson, Niklas; Ossenkoppele, Rik; Smith, Ruben Alzheimer's Research & Therapy, Vol. 10, Issue 1 https://doi.org/10.1186/s13195-018-0403-x	journal	August 2018
A walk through tau therapeutic strategies. Jadhav, Santosh; Avila, Jesus; Schöll, Michael Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.39320	text	January 2019
The Relation Between Brain Amyloid Deposition, Cortical Atrophy, and Plasma Biomarkers in Amnesic Mild Cognitive Impairment and Alzheimer’s Disease Fan, Ling-Yun; Tzen, Kai-Yuan; Chen, Ya-Fang Frontiers in Aging Neuroscience, Vol. 10 https://doi.org/10.3389/fnagi.2018.00175	journal	June 2018
Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response Bachiller, Sara; Jiménez-Ferrer, Itzia; Paulus, Agnes Frontiers in Cellular Neuroscience, Vol. 12 https://doi.org/10.3389/fncel.2018.00488	journal	December 2018
Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain DeVos, Sarah L.; Corjuc, Bianca T.; Oakley, Derek H. Frontiers in Neuroscience, Vol. 12 https://doi.org/10.3389/fnins.2018.00267	journal	April 2018
Molecular Bases of Neurodegeneration and Cognitive Decline, the Major Burden of Sanfilippo Disease Heon-Roberts, Rachel; Nguyen, Annie L. A.; Pshezhetsky, Alexey V. Journal of Clinical Medicine, Vol. 9, Issue 2 https://doi.org/10.3390/jcm9020344	journal	January 2020
Regional multimodal relationships between tau, hypometabolism, atrophy, and fractional anisotropy in atypical Alzheimer's disease Sintini, Irene; Schwarz, Christopher G.; Martin, Peter R. Human Brain Mapping https://doi.org/10.1002/hbm.24473	journal	December 2018
Questions concerning the role of amyloid-β in the definition, aetiology and diagnosis of Alzheimer’s disease Morris, Gary P.; Clark, Ian A.; Vissel, Bryce Acta Neuropathologica, Vol. 136, Issue 5 https://doi.org/10.1007/s00401-018-1918-8	journal	October 2018
Influence of hippocampal GABAB receptor inhibition on memory in rats with acute β-amyloid toxicity Almasi, Azam; Zarei, Mohammad; Raoufi, Safoura Metabolic Brain Disease, Vol. 33, Issue 6 https://doi.org/10.1007/s11011-018-0292-5	journal	July 2018
Tau pathology in cognitively normal older adults Ziontz, Jacob; Bilgel, Murat; Shafer, Andrea T. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol. 11, Issue 1 https://doi.org/10.1016/j.dadm.2019.07.007	journal	December 2019
Molecular imaging in dementia: Past, present, and future Laforce, Robert; Soucy, Jean-Paul; Sellami, Leila Alzheimer's & Dementia, Vol. 14, Issue 11 https://doi.org/10.1016/j.jalz.2018.06.2855	journal	July 2018
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
Lifespan Changes of the Human Brain In Alzheimer’s Disease Coupé, Pierrick; Manjón, José Vicente; Lanuza, Enrique Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-39809-8	journal	March 2019
Plasma tau/amyloid-β1–42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease Park, Jong-Chan; Han, Sun-Ho; Yi, Dahyun Brain, Vol. 142, Issue 3 https://doi.org/10.1093/brain/awy347	journal	January 2019
Plasma tau/amyloid-β_1–42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease [Correction] No authors listed Brain, Vol. 142, Issue 5, p. e19- https://doi.org/10.1093/brain/awz033	journal	February 2019
Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET La Joie, Renaud; Visani, Adrienne V.; Baker, Suzanne L. Science Translational Medicine, Vol. 12, Issue 524 https://doi.org/10.1126/scitranslmed.aau5732	journal	January 2020
Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer’s disease spectrum Timmers, Tessa; Ossenkoppele, Rik; Wolters, Emma E. Alzheimer's Research & Therapy, Vol. 11, Issue 1 https://doi.org/10.1186/s13195-019-0510-3	journal	July 2019
Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice Davtyan, Hayk; Hovakimyan, Armine; Kiani Shabestari, Sepideh Alzheimer's Research & Therapy, Vol. 11, Issue 1 https://doi.org/10.1186/s13195-019-0556-2	journal	December 2019
A walk through tau therapeutic strategies Jadhav, Santosh; Avila, Jesus; Schöll, Michael Acta Neuropathologica Communications, Vol. 7, Issue 1 https://doi.org/10.1186/s40478-019-0664-z	journal	February 2019
Key Peptides and Proteins in Alzheimer’s Disease Penke, Botond; Bogár, Ferenc; Paragi, Gábor Current Protein & Peptide Science, Vol. 20, Issue 6 https://doi.org/10.2174/1389203720666190103123434	journal	May 2019
Heparan Sulfate as a Therapeutic Target in Tauopathies: Insights From Zebrafish Alavi Naini, Seyedeh Maryam; Soussi-Yanicostas, Nadia Frontiers in Cell and Developmental Biology, Vol. 6 https://doi.org/10.3389/fcell.2018.00163	journal	December 2018
Disrupted core-periphery structure of multimodal brain networks in Alzheimer's Disease Guillon, Jeremy; Chavez, Mario; Battiston, Federico arXiv https://doi.org/10.48550/arxiv.1811.11688	text	January 2018
Differences in topological progression profile among neurodegenerative diseases from imaging data Garbarino, Sara; Lorenzi, Marco; Oxtoby, Neil P. eLife, Vol. 8 https://doi.org/10.7554/elife.49298	journal	December 2019

Figures / Tables (9)

Similar Records

Distinct effects of beta-amyloid and tau on cortical thickness in cognitively healthy older adults

Journal Article · Mon Dec 14 23:00:00 EST 2020 · Alzheimer's & Dementia · OSTI ID:1826560

Tau accumulation and atrophy predict amyloid independent cognitive decline in aging

Journal Article · Thu Feb 08 23:00:00 EST 2024 · Alzheimer's & Dementia · OSTI ID:2470691

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Alzheimer's Disease
Amyloid imaging
Brain atrophy
Dementia
Neurosciences & Neurology
Tau imaging

Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease

Citation Formats

References (103)

Cited By (28)

Figures / Tables (9)

Similar Records

Related Subjects