Clinicopathologic Correlations in a Large Alzheimer Disease Center Autopsy Cohort: Neuritic Plaques and Neurofibrillary Tangles "Do Count" When Staging Disease Severity
Open accessAbstract
There is uncertainty regarding the association of cognitive decline in Alzheimer disease (AD) with classic histopathologic features- neurofibrillary tangles (NFTs) and "neuritic" amyloid plaques (NPs). This uncertainty fuels doubts about the diagnostic importance of NFTs and NPs and leads to confusion regarding hypotheses of AD pathogenesis. Three hundred ninety subjects who underwent longitudinal premortem clinical workup and postmortem quantitative neuropathologic assessment served as the group to address this issue. Subjects with concomitant brain disease(s) were analyzed independently to more accurately assess the contribution of distinct pathologies to cognitive decline. More than 60% of patients of all age groups had important non-AD brain pathologies. However, subjects without superimposed brain diseases showed strong correlations between AD-type pathology counts (NFTs > NPs) and premortem Mini-Mental State Examination scores. The observed correlation was stronger in isocortex than in allocortex and was maintained across age groups including patients older than 90 years. A theoretical model is proposed in which our results are interpreted to support the "amyloid cascade hypothesis" of AD pathogenesis. Our data show that there are many important contributory causes to cognitive decline in older persons. However, NFTs and NPs should not be dismissed as irrelevant in AD based on clinicopathologic correlation.
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?
AD neuropathologic change is documented in approximately 80% of cases with a traditional clinical diagnosis of "AD dementia".
“AD neuropathologic change is documented in approximately 80% of cases with a traditional clinical diagnosis of “AD dementia” (see Fig. 5 for an example of clinical misdiagnosis of “AD dementia”) [50–52,162,185,209–211].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [209]
The Discussion reports a relationship between AD pathology and premortem cognitive decline, and the ‘Clinicopathologic Correlation in a Theoretical Context’ section reports how often dementia and abundant plaques and tangles co-occur in a selected group. Neither passage gives the proportion of patients with a traditional clinical diagnosis of AD dementia who had AD neuropathologic change at autopsy. Searches for clinical-diagnosis accuracy and an 80% figure found no such result in our copy; page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn humans, tau aggregation and the presence of NFTs correlate more closely with symptom severity and neuron loss than do Aβ lesions.
“Overall, in humans, tau aggregation and the presence of NFTs correlate more closely with symptom severity and neuron loss than do Aβ lesions49.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [49]
AD pathology (mainly neurofibrillary tangles and neuritic plaques) is the main morphological substrate of clinical dementia.
“These data add further evidence for AD pathology (mainly neurofibrillary tangles and neuritic plaques) being the main morphological substrate of clinical dementia [51],[79],[80].”
From The overlap between vascular disease and Alzheimer’s disease - lessons from pathology (2014) · cites this paper as [79]
Even in extreme old age, the presence of many neocortical NFTs correlates with antemortem cognitive decline.
“Even in extreme old age, the presence of many neocortical NFTs correlates with antemortem cognitive decline (105, 188-191).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [189]
Together, these and perhaps other uncharacterized changes may weaken the apparent association between AD pathologic diagnosis and cognitive status.
“Together, these and perhaps other uncharacterized changes may weaken the apparent association between AD pathologic diagnosis and cognitive status (189, 195, 198).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [189]
75% to 90% of patients older than 90 years have some degree of CVD pathologic diagnosis.
“75% to 90% of patients older than 90 years have some degree of CVD pathologic diagnosis (189, 205-207).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [189]
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
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · see citing works
RetractedThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Blessed, G., Tomlinson, B. E., & Roth, M. (1968) · British Journal of Psychiatry · doi:10.1192/bjp.114.512.797 · Cited by 4,117 · 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
Snowdon, D. A. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540340047031 · Cited by 1,590 · 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
Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease
Giannakopoulos, P., Herrmann, F. R., Bussière, T., Bouras, C., Kövari, E., Perl, D. P., Morrison, J. H., Gold, G., & Hof, P. R. (2003) · Neurology · doi:10.1212/01.wnl.0000063311.58879.01 · Cited by 1,118 · see citing works
Cairns, N. J., Bigio, E. H., Mackenzie, I. R. A., Neumann, M., Lee, V. M.-Y., Hatanpaa, K. J., White, C. L., Schneider, J. A., Grinberg, L. T., Halliday, G., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0237-2 · Cited by 1,110 · see citing works
Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.
Snowdon, D. A., Greiner, L. H., Mortimer, J. A., et al. (1997) · PubMed · Cited by 846 · 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 · see citing works
Price, J. L., Davis, P. B., Morris, J. C., & White, D. L. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90006-6 · Cited by 818 · see citing works
über eigenartige Krankheitsfälle des späteren Alters
Alzheimer, A. (1911) · Zeitschrift für die gesamte Neurologie und Psychiatrie · doi:10.1007/bf02866241 · Cited by 717 · see citing works
Berg, 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
Neuropathologic Features of Amnestic Mild Cognitive Impairment
Petersen, R. C., Parisi, J. E., Dickson, D. W., Johnson, K. A., Knopman, D. S., Boeve, B. F., Jicha, G. A., Ivnik, R. J., Smith, G. E., Tangalos, E. G., et al. (2006) · Archives of Neurology · doi:10.1001/archneur.63.5.665 · Cited by 616 · see citing works
Self-citationNeurofibrillary Tangles, Amyloid, and Memory in Aging and Mild Cognitive Impairment
Guillozet-Bongaarts, A. L., Weıntraub, S., Mash, D. C., & Mesulam, M. M. (2003) · Archives of Neurology · doi:10.1001/archneur.60.5.729 · Cited by 572 · see citing works
Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions
Bennett, D. A., Schneider, J. A., Bienias, J. L., Evans, D. A., & Wilson, R. S. (2005) · Neurology · doi:10.1212/01.wnl.0000152982.47274.9e · Cited by 537 · see citing works
Bennett, D. A., Schneider, J. A., Wilson, R. S., Bienias, J. L., & Arnold, S. E. (2004) · Archives of Neurology · doi:10.1001/archneur.61.3.378 · Cited by 526 · see citing works
Neocortical 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
Alzheimer's disease: The amyloid cascade hypothesis: An update and reappraisal
Hardy, J. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s317 · Cited by 475 · see citing works
Neuropathologic Substrate of Mild Cognitive Impairment
Markesbery, W. R., Schmitt, F. A., Kryscio, R. J., Davis, D. G., Smith, C. D., & Wekstein, D. R. (2006) · Archives of Neurology · doi:10.1001/archneur.63.1.38 · Cited by 460 · see citing works
Self-citationCerebral infarctions and the likelihood of dementia from Alzheimer disease pathology
Schneider, J. A., Wilson, R. S., Bienias, J. L., Evans, D. A., & Bennett, D. A. (2004) · Neurology · doi:10.1212/01.wnl.0000118211.78503.f5 · Cited by 436 · see citing works
The Neuropathology of Alcohol-specific Brain Damage, or Does Alcohol Damage the Brain?
Harper, C. G. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199802000-00001 · Cited by 405 · see citing works
Neuropathologic Outcome of Mild Cognitive Impairment Following Progression to Clinical Dementia
Jicha, G. A., Parisi, J. E., Dickson, D. W., Johnson, K., Cha, R., Ivnik, R. J., Tangalos, E. G., Boeve, B. F., Knopman, D. S., Braak, H., et al. (2006) · Archives of Neurology · doi:10.1001/archneur.63.5.674 · Cited by 399 · see citing works
Self-citationA4 amyloid protein deposition and the diagnosis of Alzheimer's disease
Davies, L., Wolska, B., Hilbich, C., Multhaup, G., Martins, R. N., Simms, G., Beyreuther, K. T., & Masters, C. L. (1988) · Neurology · doi:10.1212/wnl.38.11.1688 · Cited by 369 · 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-citationCerebrovascular Pathology and Dementia in Autopsied Honolulu‐Asia Aging Study Participants
WHITE, L., PETROVITCH, H., HARDMAN, J., NELSON, J., DAVIS, D. G., ROSS, G. W., MASAKI, K., LAUNER, L., & MARKESBERY, W. R. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04794.x · Cited by 357 · see citing works
Self-citationWirths, O., Multhaup, G., & Bayer, T. A. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02737.x · Cited by 349 · see citing works
Bancher, C., Braak, H., Fischer, P., & Jellinger, K. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90590-h · Cited by 314 · see citing works
ROTH, M., TOMLINSON, B. E., & BLESSED, G. (1966) · Nature · doi:10.1038/209109a0 · Cited by 298 · see citing works
Nagy, Z., Esiri, M. M., Jobst, K. A., Morris, J. H., King, E. M.-F., McDonald, B., Litchfield, S., Smith, A. D., Barnetson, L. P. D., & Smith, A. D. (1995) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000106918 · Cited by 283 · see citing works
Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons
Schneider, J. A., Boyle, P. A., Arvanitakis, Z., Bienias, J. L., & Bennett, D. A. (2007) · Annals of Neurology · doi:10.1002/ana.21142 · Cited by 264 · see citing works
Mitchell, T. W., Mufson, E. J., Schneider, J. A., Cochran, E. J., Nissanov, J., Han, L., Bienias, J. L., Lee, V. M. ‐., Trojanowski, J. Q., Bennett, D. A., et al. (2002) · Annals of Neurology · doi:10.1002/ana.10086 · Cited by 249 · see citing works
Cognitive impact of subcortical vascular and Alzheimer’s disease pathology
Chui, H. C., Zarow, C., Mack, W. J., Ellis, W. G., Zheng, L., Jagust, W. J., Mungas, D., Reed, B. R., Kramer, J. H., DeCarli, C. C., et al. (2006) · Annals of Neurology · doi:10.1002/ana.21009 · Cited by 247 · see citing works
Mirra, S. S. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00058-4 · Cited by 236 · see citing works
Memory and mental status correlates of modified Braak staging
Grober, E. H., Dickson, D. W., Sliwinski, M. J., Herman Buschke, L., Katz, M., Crystal, H., & Lipton, R. B. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00063-9 · Cited by 235 · see citing works
AD lesions and infarcts in demented and non‐demented Japanese‐American men
Petrovitch, H., Ross, G. W., Steinhorn, S. C., Abbott, R. D., Markesbery, W., Davis, D., Nelson, J., Hardman, J., Masaki, K., Vogt, M. R., et al. (2005) · Annals of Neurology · doi:10.1002/ana.20318 · Cited by 230 · see citing works
Self-citationThe Effects of Additional Pathology on the Cognitive Deficit in Alzheimer Disease
Nagy, Z., Esiri, M. M., Jobst, K. A., Morris, J. H., King, E. M.-F., McDonald, B., Joachim, C. L., Litchfield, S., Barnetson, L. P. D., & Smith, A. D. (1997) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199702000-00007 · Cited by 218 · see citing works
Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease
Haroutunian, V., Purohit, D. P., Perl, D. P., Marin, D., Khan, K., Lantz, M., Davis, K. L., & Mohs, R. C. (1999) · Archives of Neurology · doi:10.1001/archneur.56.6.713 · Cited by 201 · see citing works
Risk factors for transitions from normal to mild cognitive impairment and dementia
Kryscio, R. J., Schmitt, F. A., Salazar-Uribe, J. C., Mendiondo, M. S., & Markesbery, W. R. (2006) · Neurology · doi:10.1212/01.wnl.0000203264.71880.45 · Cited by 173 · see citing works
Self-citationArai, Y., Yamazaki, M., Mori, O., Muramatsu, H., Asano, G., & Katayama, Y. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03082-1 · Cited by 173 · see citing works
MIRRA, S. S., GEARING, M., MCKEEL, D. W., CRAIN, B. J., HUGHES, J. P., BELLE, G. V., & HEYMAN, A. (1994) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199405000-00012 · Cited by 156 · see citing works
White, L., Small, B. J., Petrovitch, H., Ross, G. W., Masaki, K., Abbott, R. D., Hardman, J., Davis, D., Nelson, J., & Markesbery, W. (2005) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988705281872 · Cited by 155 · see citing works
Self-citationAβ as a bioflocculant: implications for the amyloid hypothesis of Alzheimer’s disease
Robinson, S. R., & Bishop, G. M. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00342-6 · Cited by 153 · see citing works
Amyloid-β in Alzheimer Disease: The Null versus the Alternate Hypotheses
Lee, H., Zhu, X., Castellani, R. J., Nunomura, A., Perry, G. L., & Smith, M. A. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.114009 · Cited by 139 · see citing works
Accuracy of clinical criteria for AD in the Honolulu–Asia Aging Study, a population-based study
Petrovitch, H., White, L. R., Ross, G. W., Steinhorn, S. C., Li, C. Y., Masaki, K., Davis, D. G., Nelson, J., Hardman, J. M., Curb, J. D., et al. (2001) · Neurology · doi:10.1212/wnl.57.2.226 · Cited by 136 · see citing works
Self-citationNeuropathology of Alzheimer disease: pathognomonic but not pathogenic
Castellani, R. J., Lee, H., Zhu, X., Nunomura, A., Perry, G. L., & Smith, M. A. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0071-y · Cited by 133 · see citing works
Bancher, 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
Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease
Prohovnik, I., Perl, D. P., Davis, K. L., Libow, L. S., Lesser, G. T., & Haroutunian, V. H. (2006) · Neurology · doi:10.1212/01.wnl.0000191298.68045.50 · Cited by 129 · see citing works
Clinical validity of Braak neuropathological staging in the oldest-old
Gold, G., Bouras, C., Kövari, E., Canuto, A., González Glaría, B., Malky, A., Hof, P. R., Michel, J.-P., & Giannakopoulos, P. (2000) · Acta Neuropathologica · doi:10.1007/s004010051163 · Cited by 128 · see citing works
Attems, J., Quass, M., Jellinger, K. A., & Lintner, F. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.013 · Cited by 119 · see citing works
AD brain pathology: Vascular origins?
Launer, L. J., Petrovitch, H., Ross, G. W., Markesbery, W., & White, L. R. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.03.008 · Cited by 117 · see citing works
Self-citationHansen, L. A., Masliah, E., Terry, R. D., & Mirra, S. S. (1989) · Acta Neuropathologica · doi:10.1007/bf00688209 · Cited by 115 · see citing works
Xuereb, J. H., Brayne, C., Dufouil, C., Gertz, H.-J., Wischik, C. M., Harrington, C. R., Mukaetova‐Ladinska, E. B., McGee, M. A., O'SULLIVAN, A., O’Connor, D., et al. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06404.x · Cited by 113 · see citing works
Wolf, D. S., Gearing, M., Snowdon, D. A., Mori, H., Markesbery, W. R., & Mirra, S. S. (1999) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199910000-00009 · Cited by 112 · see citing works
Self-citationNeuropathology of Alzheimer's disease and other dementias
Dickson, D. W. (2001) · Clinics in Geriatric Medicine · doi:10.1016/s0749-0690(05)70066-5 · Cited by 110 · see citing works
Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?
Imhof, A., Kövari, E., von Gunten, A., Gold, G., Rivara, C.-B., Herrmann, F. R., Hof, P. R., Bouras, C., & Giannakopoulos, P. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.025 · Cited by 106 · see citing works
Neuropathological background of twenty-seven centenarian brains
Mizutani, T., & Shimada, H. (1992) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(92)90047-o · Cited by 106 · see citing works
Mungas, D., Reed, B. R., Ellis, W. G., & Jagust, W. J. (2001) · Archives of Neurology · doi:10.1001/archneur.58.8.1243 · Cited by 104 · 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
Comparison of neuropathologic criteria for the diagnosis of Alzheimer's disease
Geddes, J. W., Tekirian, T. L., Soultanian, N. S., Ashford, J. W., Davis, D. G., & Markesbery, W. R. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00063-8 · Cited by 101 · see citing works
Self-citationGiannakopoulos, P., Gold, G., Kövari, E., von Gunten, A., Imhof, A., Bouras, C., & Hof, P. R. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0144-y · Cited by 95 · see citing works
Hogervorst, E., Bandelow, S., Combrinck, M. I., Irani, S. R., & Smith, A. D. (2003) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000071006 · Cited by 78 · see citing works
Giannakopoulos, P., Hof, P. R., Giannakopoulos, A.-S., Herrmann, F. R., Michel, J.-P., & Bouras, C. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540360028012 · Cited by 78 · see citing works
Marchesi, V. T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503181102 · Cited by 74 · see citing works
McKeel, D. W., Price, J. L., Miller, J. P., Grant, E. A., Xiong, C., Berg, L., & Morris, J. C. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.10.1028 · Cited by 68 · see citing works
Diagnosis and Staging of Alzheimer Disease
Duyckaerts, C. J., & Hauw, J. J. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00067-5 · Cited by 65 · see citing works
Alzheimer disease without neocortical neurofibrillary tangles
Tiraboschi, P., Sabbagh, M. N., Hansen, L. A., Salmon, D. P., Merdes, A., Gamst, A. C., Masliah, E., Alford, M. F., Thal, L. J., & Corey‐Bloom, J. (2004) · Neurology · doi:10.1212/01.wnl.0000118212.41542.e7 · Cited by 62 · see citing works
Amyloid‐β in Alzheimer's disease: the horse or the cart? Pathogenic or protective?
Lee, H., Castellani, R. J., Zhu, X., Perry, G. L., & Smith, M. A. (2005) · International Journal of Experimental Pathology · doi:10.1111/j.0959-9673.2005.00429.x · Cited by 61 · see citing works
Giannakopoulos, P., Hof, P. R., Surini, M., Michel, J., & Bouras, C. (1993) · Acta Neuropathologica · doi:10.1007/bf00334669 · Cited by 61 · see citing works
Corder, E. H., Woodbury, M. A., Volkmann, I., Madsen, D., Bogdanović, N., & Winblad, B. G. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00147-9 · Cited by 59 · see citing works
Halliday, G., Ng, T., Rodriguez, M., Harding, A., Blumbergs, P., Evans, W., Fabian, V., Fryer, J., Gonzales, M., Harper, C., et al. (2002) · Acta Neuropathologica · doi:10.1007/s00401-002-0529-5 · Cited by 57 · see citing works
Jicha, G. A., Petersen, R. C., Knopman, D. S., Boeve, B. F., Smith, G. E., Geda, Y. E., Johnson, K., Cha, R. H., DeLucia, M. W., Braak, H., et al. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000225312.11858.57 · Cited by 52 · see citing works
Self-citationSalazar-Uribe, J. C., Schmitt, F. A., Yu, L., Mendiondo, M. S., & Kryscio, R. J. (2005) · Statistics in Medicine · doi:10.1002/sim.2437 · Cited by 51 · see citing works
Self-citationMann, D. M. A., Jones, D., South, P. W., Snowden, J. S., & Neary, D. (1992) · Acta Neuropathologica · doi:10.1007/bf00713534 · Cited by 44 · see citing works
Neuropathology Lessons in Vascular Dementia
Chui, H. C. (2005) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000155065.31561.0a · Cited by 41 · see citing works
Sheng, B., Cheng, L. F., Law, C. B., Li, H. L., Yeung, K. M., & Lau, K. K. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01171.x · Cited by 31 · see citing works
Lippa, S. M., Lippa, C. F., & Mori, H. (2005) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/153331750502000506 · Cited by 29 · see citing works
Lewy body pathology in late-onset familial Alzheimer's disease: A clinicopathological case series
Tsuang, D. W., Riekse, R. G., Purganan, K., David, A. C., Montine, T. J., Schellenberg, G. D., Steinbart, E. J., Petrie, E. C., Bird, T. D., & Leverenz, J. B. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9302 · Cited by 24 · see citing works
Nötzold, A., Michel, K., Khattab, A. A., et al. (2006) · The Thoracic and Cardiovascular Surgeon · doi:10.1055/s-2006-924089 · Cited by 21 · see citing works
Neuropathologic diagnosis of Alzheimer disease: consensus between practicing neuropathologists?
Bancher, C., Paulus, W., Paukner, K., & Jellinger, K. A. (1997) · PubMed · Cited by 19 · see citing works
Clinical validity of Braak staging in the oldest-old
Jellinger, K. A. (2000) · Acta Neuropathologica · doi:10.1007/s004010051164 · Cited by 16 · see citing works
Savory, J., Ghribi, O., & Herman, M. M. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00037-4 · Cited by 14 · see citing works
Advances in Vascular Cognitive Impairment 2005
Chui, H. C., & Skoog, I. G. (2006) · Stroke · doi:10.1161/01.str.0000200556.18993.9a · Cited by 10 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Mendiondo MS, Ashford JW, Kryscio RJ, et al. Modelling Mini-Mental State Examination changes in Alzheimer's disease. Stat Med 2000;19: 1607Y16
Cited by
Sorted by citations
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
Hyman, 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
Self-citationNelson, 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
“Numerous CPC studies have assessed the association between NFTs and cognitive status (38, 98, 154, 158, 162, 185, 188, 189, 191, 223 Y 232, 235 Y 240, 244, 250 Y 252, 258, 261, 264, 287 Y 296).”
BackgroundResultInfluentialSelf-citationPrimary age-related tauopathy (PART): a common pathology associated with human aging
Crary, J. F., Trojanowski, J. Q., Schneider, J. A., Abisambra, J. F., Abner, E. L., Alafuzoff, I., Arnold, S. E., Attems, J., Beach, T. G., Bigio, E. H., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1349-0 · Cited by 1,467 · see citing works
Self-citationTau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · see citing works
The neuropathology of probable Alzheimer disease and mild cognitive impairment
Schneider, J. A., Arvanitakis, Z., Leurgans, S. E., & Bennett, D. A. (2009) · Annals of Neurology · doi:10.1002/ana.21706 · Cited by 935 · see citing works
Toledo, J. B., Arnold, S. E., Raible, K., Brettschneider, J., Xie, S. X., Grossman, M., Monsell, S. E., Kukull, W. A., & Trojanowski, J. Q. (2013) · Brain · doi:10.1093/brain/awt188 · Cited by 849 · see citing works
Webster, 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
“Second, it appears that density of neuritic plaques correlates more strongly with the cognitive deficits than do “diffuse” amyloid plaques (Mckee et al., 1991; Crystal et al., 1993; Tiraboschi et al., 2004; Nelson et al., 2007a; Braak et al., 2011).”
BackgroundSelf-citationThe overlap between vascular disease and Alzheimer’s disease - lessons from pathology
Attems, J., & Jellinger, K. A. (2014) · BMC Medicine · doi:10.1186/s12916-014-0206-2 · Cited by 739 · see citing works
“These data add further evidence for AD pathology (mainly neurofibrillary tangles and neuritic plaques) being the main morphological substrate of clinical dementia [51,79,80].”
BackgroundNeuropathology 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-citationThe 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
Nelson, 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-citationPontecorvo, M. J., Devous, M. D., Navitsky, M., Lu, M., Salloway, S., Schaerf, F. W., Jennings, D., Arora, A. K., McGeehan, A., Lim, N. C., et al. (2017) · Brain · doi:10.1093/brain/aww334 · Cited by 357 · see citing works
Hippocampal sclerosis in advanced age: clinical and pathological features
Nelson, P. T., Schmitt, F. A., Lin, Y., Abner, E. L., Jicha, G. A., Patel, E., Thomason, P. C., Neltner, J. H., Smith, C. D., Santacruz, K. S., et al. (2011) · Brain · doi:10.1093/brain/awr053 · Cited by 279 · see citing works
Self-citationNelson, 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-citationImmunotherapy for Alzheimer’s disease: Key Symposium: Immunotherapy for Alzheimer’s disease
Morgan, D. (2011) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2010.02315.x · Cited by 225 · 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
Prevalence and clinical phenotype of quadruple misfolded proteins in older adults
Karanth, S., Nelson, P. T., Katsumata, Y., Kryscio, R. J., Schmitt, F. A., Fardo, D. W., Cykowski, M. D., Jicha, G. A., Van Eldik, L. J., & Abner, E. L. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.1741 · Cited by 206 · see citing works
Self-citationLong, J. M., Ray, B., & Lahiri, D. K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.366336 · Cited by 198 · see citing works
Lee, H.-K., Velazquez Sanchez, C., Chen, M., Morin, P. J., Wells, J. M., Hanlon, E. B., & Xia, W. (2016) · PLOS ONE · doi:10.1371/journal.pone.0163072 · Cited by 190 · see citing works
“New Old Pathologies”: AD, PART, and Cerebral Age-Related TDP-43 With Sclerosis (CARTS)
Nelson, P. T., Trojanowski, J. Q., Abner, E. L., Al-Janabi, O. M., Jicha, G. A., Schmitt, F. A., Smith, C. D., Fardo, D. W., Wang, W.-X., Kryscio, R. J., et al. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw033 · Cited by 158 · see citing works
Self-citationRole of the neuropathology of Alzheimer disease in dementia in the oldest-old
Haroutunian, V., Schnaider-Beeri, M., Schmeidler, J., Wysocki, M., Purohit, D. P., Perl, D. P., Libow, L. S., Lesser, G. T., Maroukian, M., & Grossman, H. T. (2008) · Archives of Neurology · doi:10.1001/archneur.65.9.1211 · Cited by 154 · see citing works
Epigenetic Silencing of Nucleolar rRNA Genes in Alzheimer's Disease
Pietrzak, M., Rempala, G., Nelson, P. T., Zheng, J.-J., & Hetman, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022585 · Cited by 155 · see citing works
Self-citationAPOE-ε2 and APOE-ε4 Correlate With Increased Amyloid Accumulation in Cerebral Vasculature
Nelson, P. T., Pious, N. M., Jicha, G. A., Wilcock, D. M., Fardo, D. W., Estus, S., & Rebeck, G. W. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31829a25b9 · Cited by 150 · see citing works
Self-citationNeuropathological and transcriptomic characteristics of the aged brain
Miller, J. A., Guillozet-Bongaarts, A., Gibbons, L. E., Postupna, N., Renz, A., Beller, A. E., Sunkin, S. M., Ng, L., Rose, S. E., Smith, K. A., et al. (2017) · eLife · doi:10.7554/elife.31126 · Cited by 134 · 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-citationIs 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-citationNelson, P. T., Abner, E. L., Schmitt, F. A., Kryscio, R. J., Jicha, G. A., Santacruz, K., Smith, C. D., Patel, E., & Markesbery, W. R. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181aacbe9 · Cited by 115 · see citing works
Self-citationGarcez, M. L., Mina, F., Bellettini-Santos, T., Carneiro, F. G., Luz, A. P., Schiavo, G. L., Andrighetti, M. S., Scheid, M. G., Bolfe, R. P., & Budni, J. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.03.010 · Cited by 102 · see citing works
Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies
Nelson, P. T., Kryscio, R. J., Jicha, G. A., Abner, E. L., Schmitt, F. A., Xu, L. O., Cooper, G., Smith, C. D., & Markesbery, W. R. (2009) · Neurology · doi:10.1212/wnl.0b013e3181bacf9e · Cited by 99 · see citing works
Self-citationHead-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948
Smith, R., Schöll, M., Leuzy, A., Jögi, J., Ohlsson, T., Strandberg, O., & Hansson, O. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04496-0 · Cited by 88 · see citing works
Self-reported head injury and risk of late-life impairment and AD pathology in an AD center cohort
Abner, E. L., Nelson, P. T., Schmitt, F. A., Browning, S. R., Fardo, D. W., Wan, L., Jicha, G. A., Cooper, G. E., Smith, C. D., Caban-Holt, A. M., et al. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000355478 · Cited by 84 · see citing works
Self-citationPreclinical AD Workgroup staging: Pathological correlates and potential challenges
Jicha, G. A., Abner, E. L., Schmitt, F. A., Kryscio, R. J., Riley, K. P., Cooper, G. E., Stiles, N., Mendiondo, M. S., Smith, C. D., Van Eldik, L. J., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.02.018 · Cited by 71 · see citing works
Self-citationNelson, P. T., Abner, E. L., Scheff, S. W., Schmitt, F. A., Kryscio, R. J., Jicha, G. A., Smith, C. D., Patel, E., & Markesbery, W. R. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2008.11.006 · Cited by 70 · see citing works
Self-citationCriteria 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
Aoki, M., Volkmann, I., Tjernberg, L. O., Winblad, B., & Bogdanovic, N. (2008) · NeuroReport · doi:10.1097/wnr.0b013e328302c858 · Cited by 53 · see citing works
“End-Stage” Neurofibrillary Tangle Pathology in Preclinical Alzheimer's Disease: Fact or Fiction?
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. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101980 · Cited by 49 · see citing works
Self-citationStaging Neurodegenerative Disorders: Structural, Regional, Biomarker, and Functional Progressions
Archer, T., Kostrzewa, R. M., Beninger, R. J., & Palomo, T. (2011) · Neurotoxicity Research · doi:10.1007/s12640-010-9190-2 · Cited by 34 · see citing works
Amyloid plaque-associated oxidative degradation of uniformly radiolabeled arachidonic acid
Furman, R., Murray, I. V. J., Schall, H. E., Liu, Q., Ghiwot, Y., & Axelsen, P. H. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00316 · Cited by 26 · see citing works
Gal, J., Katsumata, Y., Zhu, H., Srinivasan, S., Chen, J., Johnson, L. A., Wang, W.-X., Golden, L. R., Wilcock, D. M., Jicha, G. A., et al. (2022) · The American Journal of Pathology · doi:10.1016/j.ajpath.2021.11.013 · Cited by 17 · see citing works
Self-citation
- Authors
- Nelson, P. T., Jicha, G. A., Schmitt, F. A., Liu, H., Davis, D. G., Mendiondo, M. S., Abner, E. L., & Markesbery, W. R.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Nelson, Peter T.
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-12
- Volume
- 66
- Issue
- 12
- Pages
- 1136-1146
- ISSN
- 0022-3069 (ISSN-L)
- PMC
- PMC3034246
- OpenAlex
- W2038962904
- Cited by
- 292
- References
- 87
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 17 · 2023: 16 · 2022: 19 · 2021: 14 · 2020: 11 · 2019: 20 · 2018: 15 · 2017: 17 · 2016: 22 · 2015: 14 · 2014: 14 · 2013: 21 · 2012: 16
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P30AG028383)
- National Institute of Neurological Disorders and Stroke (R01NS061933, K08NS050110)
- 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
- Alzheimer's disease, clinicopathological correlation, neurofibrillary tangles, neuritic plaques, cognitive decline, amyloid hypothesis, Mini-Mental State Examination, neocortex, allocortex, older adults
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Male, Mental Status Schedule, Neurologic Examination, Neuropsychological Tests, Postmortem Changes, Severity of Illness Index, Statistics as Topic, Cohort Studies, Amyloid beta-Peptides, Neurofibrillary Tangles, Disease Progression, Neuropil Threads, Plaque, Amyloid
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
