“End-Stage” Neurofibrillary Tangle Pathology in Preclinical Alzheimer's Disease: Fact or Fiction?
Open accessAbstract
Among individuals who were cognitively intact before death, autopsies may reveal some Alzheimer's disease-type pathology. The presence of end-stage pathology in cognitively intact persons would support the hypothesis that pathological markers are epiphenomena. We assessed advanced neurofibrillary (Braak stages V and VI) pathology focusing on nondemented individuals. Data from the National Alzheimer's Coordinating Center database (n = 4,690 included initially) and from the Nun Study (n = 526 included initially) were analyzed, with antemortem information about global cognition and careful postmortem studies available from each case. Global cognition (final Mini-Mental State Examination scores (MMSE) and clinical 'dementia' status) was correlated with neuropathology, including the severity of neurofibrillary pathology (Braak stages and neurofibrillary tangle counts in cerebral neocortex). Analyses support three major findings: 1. Braak stage V cases and Braak VI cases are significantly different from each other in terms of associated antemortem cognition; 2. There is an appreciable range of pathology within the category of Braak stage VI based on tangle counts such that brains with the most neurofibrillary tangles in neocortex always had profound antemortem cognitive impairment; and 3. There was no nondemented case with final MMSE score of 30 within a year of life and Braak stage VI pathology. It may be inappropriate to combine Braak stages V and VI cases, particularly in patients with early cognitive dysfunction, since the two pathological stages appear to differ dramatically in terms of both pathological severity and antemortem cognitive status. There is no documented example of truly end-stage neurofibrillary pathology coexisting with intact cognition.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Not all Alzheimer disease cases fall within the same spatial continuum with regard to brain neurofibrillary tangle distributions.
“and that not all AD cases fall within the same spatial continuum with regard to brain NFT distributions (12, 15, 151).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [151]
Among thousands of cases from dozens of clinicopathologic studies worldwide, there has never been a report of a thoroughly documented individual with truly end-stage neocortical neurofibrillary tangle pathology who lacked antemortem cognitive impairment proximal to death.
“It is important to emphasize that, among thousands of cases from dozens of CPC studies worldwide, there never has been a report of a thoroughly documented individual with truly “end-stage” neocortical NFT pathology who lacked antemortem cognitive impairment proximal to death (142, 151).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [151]
In Braak stage VI cases where neocortical neurofibrillary tangles were most abundant, cognitive impairment was found on testing.
“In the Braak stage VI cases studied where neocortical NFTs were most abundant, cognitive impairment was found on testing (151).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [151]
There was significant variation in neurofibrillary tangle burden among Braak stage VI cases.
“However, not all Braak stage VI brains were the same; there was significant variation in NFT burden in these cases (142, 151).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [151]
Not all AD cases fall within the standard NFT distribution described by the Braak staging.
“Not all AD cases fall within the standard NFT distribution described by the Braak staging (Hof et al., 1997; Abner et al., 2011; Murray et al., 2011).”
From Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014) · cites this paper as Abner et al., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium
McKeith, I. G., Dickson, D. W., Lowe, J., Emre, M., O'Brien, J. T., Feldman, H., Cummings, J., Duda, J. E., Lippa, C., Perry, E. K., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000187889.17253.b1 · Cited by 5,069 · 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
Staging of alzheimer's disease-related neurofibrillary changes
Braak, H., & Braak, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00021-6 · Cited by 2,357 · see citing works
HYMAN, B. T., & TROJANOWSKI, J. Q. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199710000-00002 · Cited by 1,542 · see citing works
Reiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., & Osborne, D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603213341202 · Cited by 1,366 · see citing works
Neuropathology of older persons without cognitive impairment from two community-based studies
Bennett, D. A., Schneider, J. A., Arvanitakis, Z., Kelly, J. F., Aggarwal, N. T., Shah, R. C., & Wilson, R. S. (2006) · Neurology · doi:10.1212/01.wnl.0000219668.47116.e6 · Cited by 1,336 · see citing works
Mild Cognitive Impairment as a Clinical Entity and Treatment Target
Petersen, R. C., & Morris, J. C. (2005) · Archives of Neurology · doi:10.1001/archneur.62.7.1160 · Cited by 935 · see citing works
Staging of Alzheimer-Related Cortical Destruction
Braak, H., Braak, E., & Bohl, J. (2008) · European Neurology · doi:10.1159/000116984 · Cited by 836 · cited 1× · see citing works
“ogy is graded using Braak staging, an ordinal 0–VI scale as defined by Braak and Braak [10, 11].”
The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease.
Delacourte, A., David, J. P., Sergeant, N., Buée, L., Wattez, A., Vermersch, P., Ghozali, F., Fallet-Bianco, C., Pasquier, F., Lebert, F., et al. (1999) · Neurology · doi:10.1212/wnl.52.6.1158 · Cited by 828 · see citing works
Snowdon, D. A. (1996) · JAMA · doi:10.1001/jama.1996.03530310034029 · Cited by 696 · see citing works
Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease
Price, J. L., McKeel, D. W., Buckles, V. D., Roe, C. M., Xiong, C., Grundman, M., Hansen, L. A., Petersen, R. C., Parisi, J. E., Dickson, D. W., et al. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.04.002 · Cited by 661 · see citing works
Self-citationBerg, L., McKeel, D. W., Miller, J. P., Storandt, M., Rubin, E. H., Morris, J. C., Baty, J., Coats, M., Norton, J., Goate, A. M., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.3.326 · Cited by 657 · see citing works
Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship
Nelson, P. T., Braak, H., & Markesbery, W. R. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181919a48 · Cited by 643 · see citing works
Self-citationNeocortical Neurofibrillary Tangles Correlate With Dementia Severity in Alzheimer's Disease
Bierer, L. M., Hof, P. R., Purohit, D. P., Carlin, L., Schmeidler, J., Davis, K. L., & Perl, D. P. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540250089017 · Cited by 514 · see citing works
The importance of neuritic plaques and tangles to the development and evolution of AD
Tiraboschi, P., Hansen, L. A., Thal, L. J., & Corey-Bloom, J. (2004) · Neurology · doi:10.1212/01.wnl.0000129697.01779.0a · Cited by 477 · see citing works
Alafuzoff, I., Arzberger, T., Al‐Sarraj, S., Bodi, I., Bogdanovic, N., Braak, H., Bugiani, O., Del‐Tredici, K., Ferrer, I., Gelpi, E., et al. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00147.x · Cited by 467 · see citing works
Pathological correlates of dementia in a longitudinal, population‐based sample of aging
Sonnen, J. A., Larson, E. B., Crane, P. K., Haneuse, S., Li, G., Schellenberg, G. D., Craft, S., Leverenz, J. B., & Montine, T. J. (2007) · Annals of Neurology · doi:10.1002/ana.21208 · Cited by 432 · see citing works
Riley, K. P., Snowdon, D. A., & Markesbery, W. R. (2002) · Annals of Neurology · doi:10.1002/ana.10161 · Cited by 392 · see citing works
MRI correlates of neurofibrillary tangle pathology at autopsy: A voxel-based morphometry study
Whitwell, J. L., Josephs, K. A., Murray, M. E., Kantarci, K., Przybelski, S. A., Weigand, S. D., Vemuri, P., Senjem, M. L., Parisi, J. E., Knopman, D. S., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000324924.91351.7d · Cited by 376 · see citing works
The Neuropathology of Older Persons with and Without Dementia from Community versus Clinic Cohorts
Schneider, J. A., Aggarwal, N. T., Barnes, L., Boyle, P., & Bennett, D. A. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-1227 · Cited by 372 · see citing works
“Preclinical” AD revisited: Neuropathology of cognitively normal older adults
Schmitt, F. A., Davis, D. G., Wekstein, D. R., Smith, C. D., Ashford, J. W., & Markesbery, W. R. (2000) · Neurology · doi:10.1212/wnl.55.3.370 · Cited by 369 · see citing works
Self-citationThe National Alzheimer's Coordinating Center (NACC) Database: an Alzheimer disease database.
Beekly, D. L., Ramos, E. M., van Belle, G., Deitrich, W. D., Clark, A. D., Jacka, M. E., & Kukull, W. A. (2004) · PubMed · Cited by 345 · see citing works
Nelson, P. T., Jicha, G. A., Schmitt, F. A., Liu, H., Davis, D. G., Mendiondo, M. S., Abner, E. L., & Markesbery, W. R. (2007) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/nen.0b013e31815c5efb · Cited by 292 · see citing works
Self-citationNeuropathological evaluation of mixed dementia
Jellinger, K. A., & Attems, J. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.045 · Cited by 273 · see citing works
Nelson, P. T., Abner, E. L., Schmitt, F. A., Kryscio, R. J., Jicha, G. A., Smith, C. D., Davis, D. G., Poduska, J. W., Patel, E., Mendiondo, M. S., et al. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00244.x · Cited by 239 · see citing works
Self-citationMirra, S. S. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00058-4 · Cited by 236 · see citing works
Neurodegenerative basis of age-related cognitive decline
Wilson, R. S., Leurgans, S. E., Boyle, P. A., Schneider, J. A., & Bennett, D. A. (2010) · Neurology · doi:10.1212/wnl.0b013e3181f39adc · Cited by 234 · see citing works
A critical evaluation of current staging of α-synuclein pathology in Lewy body disorders
Jellinger, K. A. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.07.006 · Cited by 229 · see citing works
Nitration of Tau Protein Is Linked to Neurodegeneration in Tauopathies
Horiguchi, T., Uryu, K., Giasson, B. I., Ischiropoulos, H., Lightfoot, R. T., Bellmann, C., Richter‐Landsberg, C., Lee, V. M. ‐., & Trojanowski, J. Q. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63462-1 · Cited by 220 · see citing works
Amyloid-β and τ serve antioxidant functions in the aging and Alzheimer brain
Smith, M. A., Casadesús, G., Joseph, J. A., & Perry, G. L. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)01021-3 · Cited by 189 · see citing works
Alzheimer disease pathology as a host response
Castellani, R. J., Lee, H.-G., Zhu, X., Perry, G., & Smith, M. A. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318177eaf4 · Cited by 171 · see citing works
Modeling the Relation Between Neurofibrillary Tangles and Intellectual Status
Duyckaerts, C. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)80306-5 · Cited by 150 · see citing works
Factors associated with resistance to dementia despite high Alzheimer disease pathology
Erten‐Lyons, D., Woltjer, R. L., Dodge, H. H., Nixon, R. A., Vorobik, R., Calvert, J. F., Leahy, M., Montine, T. J., & Kaye, J. A. (2009) · Neurology · doi:10.1212/01.wnl.0000341273.18141.64 · Cited by 148 · see citing works
Association between male gender and cortical Lewy body pathology in large autopsy series
Nelson, P. T., Schmitt, F. A., Jicha, G. A., Kryscio, R. J., Abner, E. L., Smith, C. D., Van Eldik, L. J., & Markesbery, W. R. (2010) · Journal of Neurology · doi:10.1007/s00415-010-5630-4 · Cited by 131 · see citing works
Self-citationBancher, C., Jellinger, K., Lassmann, H., Fischer, P., & Leblhuber, F. (1996) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/bf02189115 · Cited by 130 · see citing works
Cognitive deficits in preclinical Alzheimer's disease
Small, B. J., Mobly, J. L., Laukka, E. J., Jones, S., & Bäckman, L. (2003) · Acta Neurologica Scandinavica · doi:10.1034/j.1600-0404.107.s179.6.x · Cited by 110 · see citing works
Jicha, G. A., & Carr, S. A. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1237 · Cited by 102 · see citing works
Self-citationNeural substrates of cognitive and behavioral deficits in atypical Alzheimer's disease
von Gunten, A., Bouras, C., Kövari, E., Giannakopoulos, P., & Hof, P. R. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.11.003 · Cited by 75 · see citing works
Age, Alzheimer's disease and dementia in the Baltimore Longitudinal Study of Ageing
Dolan, D., Troncoso, J., Resnick, S. M., Crain, B. J., Zonderman, A. B., & O'Brien, R. J. (2010) · Brain · doi:10.1093/brain/awq141 · Cited by 70 · see citing works
Gertz, H., Xuereb, J. H., Huppert, F. A., Brayne, C., McGee, M. A., Paykel, E. S., Harrington, C. R., Mukaetova-Ladinska, E., Arendt, T., & Wischik, C. M. (1998) · Acta Neuropathologica · doi:10.1007/s004010050780 · Cited by 69 · see citing works
Iwakiri, M., Mizukami, K., Ikonomović, M. D., Ishikawa, M., Hidaka, S., Abrahamson, E. E., DeKosky, S. T., & Asada, T. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-0985-9 · Cited by 64 · see citing works
Caselli, R. J., Osborne, D., Reiman, E. M., Hentz, J. G., Barbieri, C. J., Saunders, A. M., Hardy, J., Graff‐Radford, N. R., Hall, G. R., & Alexander, G. E. (2001) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(01)00577-9 · Cited by 61 · see citing works
Criteria for the neuropathological diagnosis of dementing disorders: routes out of the swamp?
Jellinger, K. A. (2009) · Acta Neuropathologica · doi:10.1007/s00401-008-0466-z · Cited by 60 · see citing works
Nonsteroidal anti-inflammatory drugs are associated with increased neuritic plaques
Sonnen, J. A., Larson, E. B., Walker, R. L., Haneuse, S., Crane, P. K., Gray, S. L., Breitner, J. C. S., & Montine, T. J. (2010) · Neurology · doi:10.1212/wnl.0b013e3181f52db1 · Cited by 57 · see citing works
Is there a neuropathology difference between mild cognitive impairment and dementia?
Haroutunian, V. H., Hoffman, L. B., & Been, M. S. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.2/vharoutunian · Cited by 49 · see citing works
Clinical Features of Mild Cognitive Impairment Differ in the Research and Tertiary Clinic Settings
Jicha, G. A., Abner, E. L., Schmitt, F. A., Cooper, G. E., Stiles, N. J., Hamon, R., Carr, S., Smith, C. D., & Markesbery, W. R. (2008) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000151635 · Cited by 37 · see citing works
Self-citationMizuno, Y., Ikeda, K., Tsuchiya, K., Ishihara, R., & Shibayama, H. (2003) · Neuropathology · doi:10.1046/j.1440-1789.2003.00514.x · Cited by 21 · see citing works
Berlau, D. J., Kahle-Wrobleski, K., Head, E., Goodus, M., Kim, R., & Kawas, C. (2007) · Archives of Neurology · doi:10.1001/archneur.64.8.1193
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
“…of no reported case of truly intact cognition despite extremely severe AD pathologic changes (i.e. widespread neocortical NFTs) measured with quantitative pathologic analysis, although many persons with intact cognition have been assessed in autopsy series (33, 42, 54, 133, 142, 148, 151 Y 166).”
BackgroundInfluentialSelf-citationLimbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report
Nelson, P. T., Dickson, D. W., Trojanowski, J. Q., Jack, C. R., Boyle, P. A., Arfanakis, K., Rademakers, R., Alafuzoff, I., Attems, J., Brayne, C., et al. (2019) · Brain · doi:10.1093/brain/awz099 · Cited by 1,547 · see citing works
Self-citationWebster, S. J., Bachstetter, A. D., Nelson, P. T., Schmitt, F. A., & Van Eldik, L. J. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00088 · Cited by 755 · see citing works
“Not all AD cases fall within the standard NFT distribution described by the Braak staging (Hof et al., 1997; Abner et al., 2011; Murray et al., 2011).”
BackgroundSelf-citationNelson, P. T., Head, E., Schmitt, F. A., Davis, P. R., Neltner, J. H., Jicha, G. A., Abner, E. L., Smith, C. D., Van Eldik, L. J., Kryscio, R. J., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0826-y · Cited by 365 · see citing works
Self-citationNon-invasive assessment of Alzheimer’s disease neurofibrillary pathology using 18F-THK5105 PET
Okamura, N., Furumoto, S., Fodero‐Tavoletti, M. T., Mulligan, R. S., Harada, R., Yates, P. A., Pejoska, S., Kudo, Y., Masters, C. L., Yanai, K., et al. (2014) · Brain · doi:10.1093/brain/awu064 · Cited by 266 · see citing works
Mild cognitive impairment: pathology and mechanisms
Mufson, E. J., Binder, L. I., Counts, S., DeKosky, S. T., deToledo‐Morrell, L., Ginsberg, S. D., Ikonomović, M. D., Perez, S. E., & Scheff, S. W. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0884-1 · Cited by 258 · see citing works
Besser, L. M., Kukull, W. A., Teylan, M. A., Bigio, E. H., Cairns, N. J., Kofler, J. K., Montine, T. J., Schneider, J. A., & Nelson, P. T. (2018) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nly049 · Cited by 224 · see citing works
Self-citationRelation of neuropathology to cognition in persons without cognitive impairment
Bennett, D. A., Wilson, R. S., Boyle, P. A., Buchman, A. S., & Schneider, J. A. (2012) · Annals of Neurology · doi:10.1002/ana.23654 · Cited by 220 · see citing works
Morris, G. P., Clark, I. A., & Vissel, B. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1918-8 · Cited by 212 · see citing works
Altered Proteins in the Aging Brain
Elobeid, A., Libard, S., Leino, M., Popova, S. N., & Alafuzoff, I. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw002 · Cited by 202 · see citing works
Schmitt, F. A., Nelson, P. T., Abner, E. L., Scheff, S. W., Jicha, G. A., Smith, C. D., Cooper, G. E., Mendiondo, M. S., Danner, D. D., Eldik, L. J. V., et al. (2012) · Current Alzheimer Research · doi:10.2174/156720512801322591 · Cited by 184 · see citing works
Self-citationSander, K., Lashley, T., Gami, P., Gendron, T., Lythgoe, M. F., Rohrer, J. D., Schott, J. M., Revesz, T., Fox, N. C., & Årstad, E. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.01.003 · Cited by 187 · see citing works
Ferrer, I. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.03.005 · Cited by 174 · see citing works
Is synaptic loss a unique hallmark of Alzheimer’s disease?
Scheff, S. W., Neltner, J. H., & Nelson, P. T. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.028 · Cited by 118 · see citing works
Self-citationThe implications of different approaches to define AT(N) in Alzheimer disease
Mattsson-Carlgren, N., Leuzy, A., Janelidze, S., Palmqvist, S., Stomrud, E., Strandberg, O., Smith, R., & Hansson, O. (2020) · Neurology · doi:10.1212/wnl.0000000000009485 · Cited by 114 · see citing works
MicroRNA in Alzheimer’s disease: an exploratory study in brain, cerebrospinal fluid and plasma
Bekris, L. M., Lutz, F., Montine, T. J., Yu, C., Tsuang, D. W., Peskind, E. R., & Leverenz, J. B. (2013) · Biomarkers · doi:10.3109/1354750x.2013.814073 · Cited by 112 · see citing works
Latimer, C. S., Burke, B. T., Liachko, N. F., Currey, H. N., Kilgore, M. D., Gibbons, L. E., Henriksen, J. C., Darvas, M., Domoto‐Reilly, K., Jayadev, S., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0743-1 · Cited by 99 · see citing works
Neuropathological approaches to cerebral aging and neuroplasticity
Jellinger, K. A., & Attems, J. (2013) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2013.15.1/kjellinger · Cited by 90 · see citing works
Neltner, J. H., Abner, E. L., Schmitt, F. A., Denison, S. K., Anderson, S., Patel, E., & Nelson, P. T. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182768de4 · Cited by 83 · see citing works
Self-citationWalker, L., & Attems, J. (2023) · Journal of Parkinson s Disease · doi:10.3233/jpd-230154 · Cited by 46 · see citing works
Kok, F. K., van Leerdam, S., & de Lange, E. C. M. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-210607 · Cited by 44 · see citing works
Triplett, J. C., Swomley, A. M., Cai, J., Klein, J. B., & Butterfield, D. A. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150417 · Cited by 39 · see citing works
Braak Stage, Cerebral Amyloid Angiopathy, and Cognitive Decline in Early Alzheimer’s Disease
Malek‐Ahmadi, M. H., Perez, S. E., Chen, K., & Mufson, E. J. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191151 · Cited by 38 · see citing works
Quantitative neuropathological assessment to investigate cerebral multi-morbidity
Attems, J., Neltner, J. H., & Nelson, P. T. (2014) · Alzheimer s Research & Therapy · doi:10.1186/s13195-014-0085-y · Cited by 32 · see citing works
Self-citationGauthreaux, K. M., Mock, C., Teylan, M., Culhane, J. E., Chen, Y., Chan, K. C. G., Katsumata, Y., Nelson, P. T., & Kukull, W. A. (2022) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlac093 · Cited by 29 · see citing works
Self-citationLuna‐Muñoz, J., Charles, R., Claude, M., Flores-Rodríguez, P., Ávila, J., Sergio, R., de la Cruz, F., Mena, R., Meraz‐Ríos, M. A., & Florán, B. (2013) · InTech eBooks · doi:10.5772/54228 · Cited by 30 · see citing works
Elevated medial temporal lobe and pervasive brain tau‐PET signal in normal participants
Lowe, V. J., Bruinsma, T. J., Min, H.-K. P., Lundt, E. S., Fang, P., Senjem, M. L., Boeve, B. F., Josephs, K. A., Pandey, M. K., Murray, M. E., et al. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.01.005 · Cited by 30 · see citing works
Walker, L., McAleese, K. E., Johnson, M. A., Khundakar, A. A., Erskine, D., Thomas, A. J., McKeith, I. G., & Attems, J. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1702-2 · Cited by 29 · see citing works
Beckmann, A., Ramirez, P., Gamez, M., Gonzalez, E. M., Mange, J. D., Bieniek, K. F., Ray, W. J., & Frost, B. E. (2023) · iScience · doi:10.1016/j.isci.2023.106152 · Cited by 24 · see citing works
Nugraha, B., Mohr, M. A., Ponti, A., Emmert, M. Y., Weibel, F., Hoerstrup, S. P., Moll, S., Certa, U., Prunotto, M., & Pantazis, P. (2017) · Scientific Reports · doi:10.1038/s41598-017-12683-y · Cited by 22 · see citing works
The Nun Study: Insights from 30 years of aging and dementia research
Clarke, K. M., Etemadmoghadam, S., Danner, B., Corbett, C., Ghaseminejad-Bandpey, A., Dopler, M. B., Parker‐Garza, J., Alhneif, M., Babu, S., Ogunbona, O. B., et al. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.14626 · Cited by 19 · see citing works
Węgiel, J., Flory, M. J., Kuchna, I., Nowicki, K., Ma, S. Y., Wegiel, J., Badmajew, E., Silverman, W. P., de Leon, M. J., Reisberg, ., et al. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx027 · Cited by 18 · see citing works
Flores-Rodríguez, P., Harrington, C. R., Wischik, C. M., Ibarra-Bracamontes, V., Zarco, N., Navarrete, A., Martínez-Maldonado, A., Guadarrama-Ortíz, P., Villanueva‐Fierro, I., Ontiveros‐Torres, M. Á., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190155 · Cited by 18 · see citing works
Jellinger, K. A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26072942 · Cited by 17 · see citing works
Challenges in the Neuropathological Diagnosis of Dementias
Jellinger, K. A. (2012) · International Journal of Neuropathology · doi:10.7726/ijn.2013.1002 · Cited by 15 · see citing works
Xu, C., Guo, J., Li, L., Wang, X., Zhou, Q., Sun, D., Zhang, S., Li, S., Ye, J., Liu, Y., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-191132 · Cited by 14 · see citing works
Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer’s disease
Nehra, G., Maloney, B. J., Smith, R. R., Chumboatong, W., Abner, E. L., Nelson, P. T., Bauer, B., & Hartz, A. M. S. (2025) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00615-8 · Cited by 13 · see citing works
Self-citationLifestyle and Alzheimer’s Disease
Bartolotti, N., & Lazarov, O. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802851-3.00007-3 · Cited by 12 · see citing works
Unraveling the mystery of citrate transporters in Alzheimer’s disease: An updated review
Mukherjee, A. G., Mishra, S., Gopalakrishnan, A. V., Kannampuzha, S., Murali, R., Wanjari, U. R., Stany, B. K., Vellingiri, B., Madhyastha, H., Deepankumar, K., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102726 · Cited by 11 · see citing works
Zhan, L., Li, J., Jew, B., & Sul, J. H. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009772 · Cited by 9 · see citing works
Calvó‐Perxas, L., Pousa, S. L., Franch, J. V., Garriga, O. T., Blankenburg, M., Febrer, L., Flaqué, M., Vallmajó, N., Aguirregomozcorta, M., Genı́s, D., et al. (2012) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000337340 · Cited by 7 · see citing works
Behavioral and Neurological Effects of Edaravone and Noscapine in Albino Wistar Rats
Rehman, M. R. H., Godad, A. P., & Doshi, G. (2023) · Experimental Aging Research · doi:10.1080/0361073x.2023.2250227 · Cited by 7 · see citing works
PARAMETRIC ESTIMATION IN COMPETING RISKS AND MULTI-STATE MODELS
Lin, Y. (2011) · UKnowledge (University of Kentucky) · Cited by 2 · see citing works
Self-citationShahidehpour, R. K., Neltner, A. M., Klusty, M. A., Corbett, W. C., Gonzalez, A. D., Gutman, D. A., Fardo, D. W., Bachstetter, A. D., Bumgardner, C., Flanagan, M. E., et al. (2026) · Brain Pathology · doi:10.1111/bpa.70102 · Cited by 1 · see citing works
Self-citationNeltner, J. H., & Nelson, P. T. (2017) · Neurodegeneration · doi:10.1002/9781118661895.ch1 · Cited by 1 · see citing works
Self-citationAbner, E. L. (2013) · UKnowledge (University of Kentucky)
Self-citationMolekularne podłoże proteinopatii: przyczyna zespołów otępiennych i zaburzeń motorycznych
Zgórzyńska, E., Krawczyk, K., Bełdzińska, P., & Walczewska, A. (2021) · Postępy Higieny i Medycyny Doświadczalnej · doi:10.5604/01.3001.0014.9513
Ashford, J. W. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734280398.793553881
Rodent models of Alzheimer’s disease
Kasza, Á. (2018) · doi:10.14232/phd.9743
- Authors
- Abner, E. L., Kryscio, R. J., Schmitt, F. A., SantaCruz, K. S., Jicha, G. A., Lin, Y., Neltner, J. M., Smith, C. D., Van Eldik, L. J., & Nelson, P. T.
- Affiliations
- University of Kentucky (US)
- University of Minnesota (US)
- Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA
- Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA
- Corresponding author
- Nelson, Peter T.
- ORCID
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2011-07-08
- Volume
- 25
- Issue
- 3
- Pages
- 445-453
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC3171001
- OpenAlex
- W1901233000
- Cited by
- 49
- References
- 50
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 1 · 2014: 4 · 2013: 4 · 2012: 7
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P30AG028383, U01AG016976)
- National Institute of Neurological Disorders and Stroke (R01NS061933)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- preclinical Alzheimer's disease, neurofibrillary tangles
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Autopsy, Brain, Cognition Disorders, Female, Humans, Male, Mental Status Schedule, Neuropsychological Tests, Severity of Illness Index, Neurofibrillary Tangles, Disease Progression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
