Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease
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Neuropathological and in vivo studies have revealed a tight relationship between tau pathology and cognitive impairment across the Alzheimer's disease spectrum. However, tau pathology is also intimately associated with neurodegeneration and amyloid pathology. The aim of the present study was therefore to assess whether grey matter atrophy and amyloid pathology contribute to the relationship between tau pathology, as measured with 18F-AV-1451-PET imaging, and cognitive deficits in Alzheimer's disease. We included 40 amyloid-positive patients meeting criteria for mild cognitive impairment due to Alzheimer's disease (n = 5) or probable Alzheimer's disease dementia (n = 35). Twelve patients additionally fulfilled the diagnostic criteria for posterior cortical atrophy and eight for logopenic variant primary progressive aphasia. All participants underwent 3 T magnetic resonance imaging, amyloid (11C-PiB) positron emission tomography and tau (18F-AV-1451) positron emission tomography, and episodic and semantic memory, language, executive and visuospatial functions assessment. Raw cognitive scores were converted to age-adjusted Z-scores (W-scores) and averaged to compute composite scores for each cognitive domain. Independent regressions were performed between 18F-AV-1451 binding and each cognitive domain, and we used the Biological Parametric Mapping toolbox to further control for local grey matter volumes, 11C-PiB uptake, or both. Partial correlations and causal mediation analyses (mediation R package) were then performed in brain regions showing an association between cognition and both 18F-AV-1451 uptake and grey matter volume. Our results showed that decreased cognitive performance in each domain was related to increased 18F-AV-1451 binding in specific brain regions conforming to established brain-behaviour relationships (i.e. episodic memory: medial temporal lobe and angular gyrus; semantic memory: left anterior temporal regions; language: left posterior superior temporal lobe and supramarginal gyrus; executive functions: bilateral frontoparietal regions; visuospatial functions: right more than left occipitotemporal regions). This pattern of regional associations remained essentially unchanged-although less spatially extended-when grey matter volume or 11C-PiB uptake maps were added as covariates. Mediation analyses revealed both direct and grey matter-mediated effects of 18F-AV-1451 uptake on cognitive performance. Together, these results show that tau pathology is related in a region-specific manner to cognitive impairment in Alzheimer's disease. These regional relationships are weakly related to amyloid burden, but are in part mediated by grey matter volumes. This suggests that tau pathology may lead to cognitive deficits through a variety of mechanisms, including, but not restricted to, grey matter loss. These results might have implications for future therapeutic trials targeting tau pathology.
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Intracellular aggregates of hyperphosphorylated Tau correlate with cognitive decline in Alzheimer's disease.
“One of the pathological hallmarks of Alzheimer’s disease is the intracellular aggregates of hyperphosphorylated Tau, which show good correlation to cognitive decline [1, 2].”
From Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons (2026) · cites this paper as [1]
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McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · see citing works
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.008 · Cited by 10,152 · cited 1× · see citing works
“, 2011) or mild cognitive impairment (MCI) due to Alzheimer’s disease (n = 5; Albert et al., 2011).”
BackgroundSelf-citationHyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668 · see citing works
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Shaw, L. M., Vanderstichele, H., Knapik‐Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., Blennow, K., Soares, H., Simon, A., Lewczuk, P., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21610 · Cited by 2,065 · see citing works
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050 · cited 3× · see citing works
“In contrast, amyloid-b pathology has only a relatively modest direct correlation with cognition (Nelson et al., 2012).”
BackgroundTwo Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease
Salloway, S., Sperling, R., Fox, N. C., Blennow, K., Klunk, W., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Ferris, S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1304839 · Cited by 1,960 · see citing works
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489 · see citing works
PET Imaging of Tau Deposition in the Aging Human Brain
Schöll, M., Lockhart, S. N., Schonhaut, D. R., O’Neil, J. P., Janabi, M., Ossenkoppele, R., Baker, S. L., Vogel, J. W., Faria, J., Schwimmer, H. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.028 · Cited by 1,214 · see citing works
Self-citationMurray, M. E., Graff-Radford, N. R., Ross, O. A., Petersen, R. C., Duara, R., & Dickson, D. W. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70156-9 · Cited by 972 · see citing works
Xia, C., Arteaga, J., Chen, G., Gangadharmath, U., Gomez, L. F., Kasi, D., Lam, C., Liang, Q., Liu, C., Mocharla, V. P., et al. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2012.11.008 · Cited by 605 · see citing works
In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum
Cho, H., Choi, J. Y., Hwang, M. S., Kim, Y. J., Lee, H. M., Lee, H. S., Lee, J. H., Ryu, Y. H., Lee, M. S., & Lyoo, C. H. (2016) · Annals of Neurology · doi:10.1002/ana.24711 · Cited by 499 · see citing works
Pathological Tau Disrupts Ongoing Network Activity
Menkes-Caspi, N., Yamin, H. G., Kellner, V., Spires-Jones, T. L., Cohen, D., & Stern, E. A. (2015) · Neuron · doi:10.1016/j.neuron.2015.01.025 · Cited by 184 · see citing works
Cognitive impact of neuronal pathology in the entorhinal cortex and CA1 field in Alzheimer's disease
GUNTEN, A., KOVARI, E., BUSSIERE, T., RIVARA, C., GOLD, G., BOURAS, C., HOF, P., & GIANNAKOPOULOS, P. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.02.008 · Cited by 101 · see citing works
Flagged first, then by citations
Research works printed but not linked: 37
- Anto ´n-Ferna ´ndez A, Aparicio-Torres G, Tapia S, DeFelipe J, Mun ˜oz A. Morphometric alterations of Golgi apparatus in Alzheimer's disease are related to tau hyperphosphorylation. Neurobiol Dis 2017; 97: 11-23.
- Arriagada PV, Marzloff K, Hyman BT. Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease. Neurology 1992b; 42: 1681-8.
- Baker SL, Lockhart SN, Price JC, He M, Huesman RH, Schonhaut D, et al. Reference tissue-based kinetic evaluation of 18F-AV-1451 for tau imaging. J Nucl Med 2017; 58: 332-8.
- Braak H, Del Tredici K. The preclinical phase of the pathological process underlying sporadic Alzheimer's disease. Brain 2015; 138: 2814-33.
- Callahan LM, Vaules WA, Coleman PD. Quantitative decrease in synaptophysin message expression and increase in cathepsin D mes- sage expression in Alzheimer disease neurons containing neurofibril- lary tangles. J Neuropathol Exp Neurol 1999; 58: 275-87.
- Che ´telat G, Desgranges B, Landeau B, Me ´zenge F, Poline JB, de la Sayette V, et al. Direct voxel-based comparison between grey matter hypometabolism and atrophy in Alzheimer's disease. Brain 2008; 131: 60-71.
- Cho H, Choi JY, Hwang MS, Lee JH, Kim YJ, Lee HM, et al. Tau PET in Alzheimer disease and mild cognitive impairment. Neurology 2016b; 87: 375-83.
- Cowan CM, Mudher A. Are tau aggregates toxic or protective in tauopathies? Front Neurol 2013; 4: 114.
- Dowling NM, Johnson SC, Gleason CE, Jagust WJ, Alzheimer's Disease Neuroimaging Initiative. The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid bio- markers and neurocognitive function. Neuroimage 2015; 105: 357- 68.
- Dronse J, Fliessbach K, Bischof GN, von Reutern B, Faber J, Hammes J, et al. In vivo patterns of tau pathology, amyloid-b burden, and neuronal dysfunction in clinical variants of Alzheimer's disease. J Alzheimers Dis 2016; 55: 465-71.
- Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol 2014; 13: 614-29.
- Gefen T, Gasho K, Rademaker A, Lalehzari M, Weintraub S, Rogalski E, et al. Clinically concordant variations of Alzheimer pathology in aphasic versus amnestic dementia. Brain 2012; 135: 1554-65.
- Giannakopoulos P, Herrmann FR, Bussie `re T, Bouras C, Ko ¨vari E, Perl DP, et al. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 2003; 60: 1495-500.
- Ginsberg SD, Hemby SE, Lee VM, Eberwine JH, Trojanowski JQ. Expression profile of transcripts in Alzheimer's disease tangle-bear- ing CA1 neurons. Ann Neurol 2000; 48: 77-87.
- Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76: 1006-14.
- Guillozet AL, Weintraub S, Mash DC, Mesulam MM. Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impair- ment. Arch Neurol 2003; 60: 729-36.
- Hof PR, Bouras C, Constantinidis J, Morrison JH. Balint's syndrome in Alzheimer's disease: specific disruption of the occipito-parietal visual pathway. Brain Res 1989; 493: 368-75.
- Jack CR, Dickson DW, Parisi JE, Xu YC, Cha RH, O'Brien PC, et al. Antemortem MRI findings correlate with hippocampal neuropathol- ogy in typical aging and dementia. Neurology 2002; 58: 750-7.
- Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J, Rentz D, et al. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol 2016; 79: 110-19.
- Katsuse O, Lin W-L, Lewis J, Hutton ML, Dickson DW. Neurofibrillary tangle-related synaptic alterations of spinal motor neurons of P301L tau transgenic mice. Neurosci Lett 2006; 409: 95-9.
- Koss DJ, Jones G, Cranston A, Gardner H, Kanaan NM, Platt B. Soluble pre-fibrillar tau and b-amyloid species emerge in early human Alzheimer's disease and track disease progression and cog- nitive decline. Acta Neuropathol 2016; 132: 875-95.
- Kramer JH, Jurik J, Sha SJ, Rankin KP, Rosen HJ, Johnson JK, et al. Distinctive neuropsychological patterns in frontotemporal dementia, semantic dementia, and Alzheimer disease. Cogn Behav Neurol 2003; 16: 211-18.
- Kuchibhotla KV, Wegmann S, Kopeikina KJ, Hawkes J, Rudinskiy N, Andermann ML, et al. Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo. Proc Natl Acad Sci USA 2014; 111: 510-14.
- Lehmann M, Ghosh PM, Madison C, Laforce R, Jr, Corbetta-Rastelli C, Weiner MW, et al. Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer's disease. Brain 2013; 136: 844-58.
- Lowe VJ, Curran G, Fang P, Liesinger AM, Josephs KA, Parisi JE, et al. An autoradiographic evaluation of AV-1451 Tau PET in de- mentia. Acta Neuropathol Commun 2016; 4: 58.
- Marquie ´M, Siao Tick Chong M, Anto ´n-Ferna ´ndez A, Verwer EE, Sa ´ez-Calveras N, Meltzer AC, et al. [F-18]-AV-1451 binding correl- ates with postmortem neurofibrillary tangle Braak staging. Acta Neuropathol 2017; 134: 619-28.
- Mendez MF, Ghajarania M, Perryman KM. Posterior cortical atrophy: clinical characteristics and differences compared to Alzheimer's dis- ease. Dement Geriatr Cogn Disord 2002; 14: 33-40.
- Mitchell TW, Mufson EJ, Schneider JA, Cochran EJ, Nissanov J, Han L-Y, et al. Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and early Alzheimer's disease. Ann Neurol 2002; 51: 182-9.
- O'Brien PC, Dyck PJ. Procedures for setting normal values. Neurology 1995; 45: 17-23.
- Ossenkoppele R, Schonhaut DR, Scho ¨ll M, Lockhart SN, Ayakta N, Baker SL, et al. Tau PET patterns mirror clinical and neuroanatom- ical variability in Alzheimer's disease. Brain 2016; 139: 1551-67.
- Price JL, Morris JC. Tangles and plaques in nondemented aging and 'preclinical' Alzheimer's disease. Ann Neurol 1999; 45: 358-68.
- Rabinovici GD, Furst AJ, Alkalay A, Racine CA, O'Neil JP, Janabi M, et al. Increased metabolic vulnerability in early-onset Alzheimer's disease is not related to amyloid burden. Brain 2010; 133: 512-28.
- Saint-Aubert L, Almkvist O, Chiotis K, Almeida R, Wall A, Nordberg A. Regional tau deposition measured by [(18)F]THK5317 positron emission tomography is associated to cognition via glucose metab- olism in Alzheimer's disease. Alzheimers Res Ther 2016; 8: 38.
- Spires-Jones TL, Hyman BT. The intersection of amyloid beta and tau at synapses in Alzheimer's disease. Neuron 2014; 82: 756-71.
- Spires-Jones TL, Kopeikina KJ, Koffie RM, de Calignon A, Hyman BT. Are tangles as toxic as they look? J Mol Neurosci 2011; 45: 438-44.
- Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991; 30: 572-80.
- Whitwell JL, Josephs KA, Murray ME, Kantarci K, Przybelski SA, Weigand SD, et al. MRI correlates of neurofibrillary tangle path- ology at autopsy: a voxel-based morphometry study. Neurology 2008; 71: 743-9.
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Machado Reyes, D., Chao, H., Hahn, J., Shen, L., Yan, P., & Initiative, F. T. A. D. N. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14040421 · Cited by 17 · see citing works
Younes, K., Smith, V., Johns, E., Carlson, M. L., Winer, J., He, Z., Henderson, V. W., Greicius, M. D., Young, C. B., & Mormino, E. C. (2024) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2024.05.002 · Cited by 13 · see citing works
Saleem, K., Xiao, Z., Zhu, B., Ren, Y., Yan, Z., & Feng, J. (2026) · Molecular Psychiatry · doi:10.1038/s41380-025-03225-4 · Cited by 10 · see citing works
“One of the pathological hallmarks of Alzheimer ’ s disease is the intracellular aggregates of hyperphosphorylated Tau, which show good correlation to cognitive decline [1, 2].”
Hantke, N. C., Kaye, J., Mattek, N., Wu, C.-Y., Dodge, H. H., Beattie, Z., & Woltjer, R. (2023) · PLOS ONE · doi:10.1371/journal.pone.0286812 · Cited by 10 · see citing works
- Authors
- Bejanin, A., Schonhaut, D. R., La Joie, R., Kramer, J. H., Baker, S. L., Sosa, N., Ayakta, N., Cantwell, A., Janabi, M., Lauriola, M., O’Neil, J. P., Gorno-Tempini, M. L., Miller, Z. A., Rosen, H. J., Miller, B. L., Jagust, W. J., & Rabinovici, G. D.
- Affiliations
- University of California, San Francisco (US)
- Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Bejanin, Alexandre
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-10-07
- Volume
- 140
- Issue
- 12
- Pages
- 3286-3300
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC5841139
- OpenAlex
- W2763470121
- Cited by
- 778
- References
- 14
- Citations by year
- 2026: 87 · 2025: 100 · 2024: 111 · 2023: 81 · 2022: 97 · 2021: 106 · 2020: 85 · 2019: 79 · 2018: 26 · 2017: 2 · 2013: 1
- FWCI
- 43.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Brain (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (R01-AG045611, R01-AG034570, P50-AG023501, P01-AG019724, U01-AG052943)
- National Institute of Neurological Disorders and Stroke (R01-NS050915, K24-DC015544)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- tau pathology, Alzheimer's disease, cognitive impairment, gray matter atrophy, amyloid pathology, 11C-PiB PET, posterior cortical atrophy, logopenic variant primary progressive aphasia, episodic memory, semantic memory, language, executive function, visuospatial ability, brain-behavior relationship, mediation
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Aniline Compounds, Brain, Carbolines, Carbon Radioisotopes, Female, Fluorine Radioisotopes, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Regression Analysis, Thiazoles, Case-Control Studies, tau Proteins, Aphasia, Primary Progressive, Positron-Emission Tomography, Benzothiazoles, Cognitive Dysfunction
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