Lewy Body Pathology in Normal Elderly Subjects
Open accessAbstract
Lewy bodies and Lewy neurites are the hallmark neuropathologic findings in Parkinson disease, Parkinson disease with dementia, dementia with Lewy bodies, and other alpha-synucleinopathies. They have also been described in the brains of normal older individuals and referred to as incidental Lewy body disease. The purpose of this study was to determine the prevalence of Lewy bodies and Lewy neurites (Lewy body pathology [LBP]) in 139 autopsies from our normal volunteer control group of the University of Kentucky Alzheimer's Disease Center. All subjects were followed longitudinally and were cognitively normal and without any type of movement disorder, neuropsychiatric features, or other CNS findings. The brains of 33 of 139 normal subjects contained LBP in various regions. The most common regions involved were the medulla (26%), amygdala (24%), pons (20%), and midbrain (20%). No mean statistical differences were found between those with and without LBP on any demographic or cognitive variable, Braak stage, or neurofibrillary tangle and neuritic plaque quantitation. An explanation for the high prevalence of LBP in our elderly, well-educated study group is not clear, although it does not seem to be related to aging or the presence of Alzheimer disease pathology. Overall, our findings support the concept that incidental Lewy body disease most likely represents preclinical or presymptomatic Parkinson disease, Parkinson disease with dementia, or dementia with Lewy bodies.
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?
Lewy-related pathology and Alzheimer's disease-type pathology have been documented in cognitively healthy individuals upon autopsy.
“LRP [74] and AD-type pathology [75] have been documented in cognitively healthy individuals upon autopsy.”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [74]
24% of the autopsied normal control cases from the University of Kentucky Alzheimer's Disease Center exhibited Lewy-related pathology.
“24% of the autopsied normal control cases from the University of Kentucky Alzheimer’s Disease Center exhibited LRP [74].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [74]
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
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777 · 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 5,105 · see citing works
Overdependence on degraded gist memory in Alzheimer's disease.
Gallo, D. A., Shahid, K. R., Olson, M. A., Solomon, T. M., Schacter, D. L., & Budson, A. E. (2006) · Neuropsychology · doi:10.1037/0894-4105.20.6.625 · Cited by 4,756 · see citing works
Moms, J. C., Heyman, A., Mohs, R. C., Hughes, J. P., van Belle, G., Fillenbaum, G., Mellits, E. D., & Clark, C. (1989) · Neurology · doi:10.1212/wnl.39.9.1159 · Cited by 4,130 · see citing works
McKeith, I. G., Galasko, D., Kosaka, K., Perry, E. K., Dickson, D. W., Hansen, L. A., Salmon, D. P., Lowe, J., Mirra, S. S., Byrne, E. J., et al. (1996) · Neurology · doi:10.1212/wnl.47.5.1113 · Cited by 3,960 · see citing works
The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.
Gibb, W. R., & Lees, A. J. (1988) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.51.6.745 · Cited by 3,481 · see citing works
The Halstead-Reitan neuropsychological test battery: Theory and clinical interpretation
Reitan, R. M., & Wolfson, D. E. (1993) · Medical Entomology and Zoology · Cited by 3,413 · see citing works
Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
Fillenbaum, G., & Heyman, A. (2002) · doi:10.1002/0470846410.ch42(iii · Cited by 2,859 · see citing works
Where Does Parkinson Disease Pathology Begin in the Brain?
Del Tredici, K., Rüb, U., de Vos, R. A. I., Bohl, J. R. E., & Braak, H. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.5.413 · Cited by 773 · see citing works
Hamilton, R. L. (2000) · Brain Pathology · doi:10.1111/j.1750-3639.2000.tb00269.x · Cited by 754 · see citing works
Neuropathology of Cognitively Normal Elderly
Knopman, D. S., Parisi, J. E., Salviati, A., Floriach-Robert, M., Boeve, B. F., Ivnik, R. J., Smith, G. E., Dickson, D. W., Johnson, K. A., Petersen, L. E., et al. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.11.1087 · Cited by 674 · see citing works
Identification of normal and pathological aging in prospectively studied nondemented elderly humans
Dickson, D. W., Crystal, H. A., Mattiace, L. A., Masur, D. M., Blau, A. D., Davies, P., Yen, S.-H., & Aronson, M. K. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90027-u · Cited by 643 · see citing works
Lippa, C. F., Fujiwara, H., Mann, D. M. A., Giasson, B., Baba, M., Schmidt, M. L., Nee, L. E., O'Connell, B., Pollen, D. A., St. George-Hyslop, P., et al. (1998) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65722-7 · Cited by 533 · see citing works
Alzheimer neuropathologic alterations in aged cognitively normal subjects
Davis, D. G., Schmitt, F. A., Wekstein, D. R., & Markesbery, W. R. (1999) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199904000-00008 · Cited by 516 · cited 1× · see citing works
“The subjects studied in this report were from the University of Kentucky Alzheimer’s Disease Center normal volunteer control group (17, 18).”
Self-citationMorris, J. C., McKeel, D. W., Storandt, M., Rubin, E. H., Price, J. L., Grant, E. A., Ball, M. J., & Berg, L. (1991) · Neurology · doi:10.1212/wnl.41.4.469 · Cited by 473 · 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-citationREM sleep behavior disorder and degenerative dementia
Boeve, B. F., Silber, M. H., Ferman, T. J., Kokmen, E., Smith, G. E., Ivnik, R. J., Parisi, J. E., Olson, E. J., & Petersen, R. C. (1998) · Neurology · doi:10.1212/wnl.51.2.363 · Cited by 392 · 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-citationAlzheimer Disease With Amygdala Lewy Bodies: A Distinct Form of α-Synucleinopathy
Uchikado, H., Lin, W.-L., DeLucia, M. W., & Dickson, D. W. (2006) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/01.jnen.0000225908.90052.07 · Cited by 359 · see citing works
Duffy, P. E., & Tennyson, V. M. (1965) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-196507000-00003 · Cited by 351 · see citing works
Neuroanatomy and Pathology of Sporadic Parkinson's Disease
Braak, H., & Tredici, K. D. (2008) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-540-79850-7 · Cited by 297 · see citing works
Lewy body-related ?-synucleinopathy in the aged human brain
Jellinger, K. A. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0138-7 · Cited by 256 · see citing works
Forno, L. S. (1969) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1969.tb01316.x · Cited by 218 · see citing works
Neuropsychologic Detection of Abnormal Mental Decline in Older Persons
Eslinger, P. J. (1985) · JAMA · doi:10.1001/jama.1985.03350290076029 · Cited by 215 · see citing works
Bowel movement frequency in late‐life and incidental Lewy bodies
Abbott, R. D., Ross, G. W., Petrovitch, H., Tanner, C. M., Davis, D. G., Masaki, K., Launer, L. J., Curb, J. D., & White, L. R. (2007) · Movement Disorders · doi:10.1002/mds.21560 · Cited by 203 · see citing works
Incidental Lewy Body Disease and Preclinical Parkinson Disease
DelleDonne, A., Klos, K. J., Fujishiro, H., Ahmed, Z., Parisi, J. E., Josephs, K. A., Frigerio, R., Burnett, M. S., Wszołek, Z. K., Uitti, R. J., et al. (2008) · Archives of Neurology · doi:10.1001/archneur.65.8.1074 · Cited by 197 · see citing works
Association of olfactory dysfunction with incidental Lewy bodies
Ross, G. W., Abbott, R. D., Petrovitch, H., Tanner, C. M., Davis, D. G., Nelson, J. R., Markesbery, W. R., Hardman, J. M., Masaki, K., Launer, L. J., et al. (2006) · Movement Disorders · doi:10.1002/mds.21076 · Cited by 194 · see citing works
Self-citationEpitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies.
Schmidt, M. L., Murray, J., Lee, V. M. Y., Hill, W. D., Wertkin, A. M., & Trojanowski, J. Q. (1991) · PubMed Central · Cited by 161 · see citing works
Mikolaenko, I., Pletniková, O., Kawas, C. H., O’Brien, R., Resnick, S. M., Crain, B. J., & Troncoso, J. C. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.156 · Cited by 159 · see citing works
Leverenz, J. B., Hamilton, R. L., Tsuang, D. W., Schantz, A. M., Vavrek, D. A., Larson, E. B., Kukull, W. A., López, O. L., Galasko, D. R., Masliah, E., et al. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00117.x · Cited by 154 · see citing works
Incidence and Extent of Lewy Body-Related α-Synucleinopathy in Aging Human Olfactory Bulb
Sengoku, R., Saito, Y., Ikemura, M., Hatsuta, H., Sakiyama, Y., Kanemaru, K., Arai, T., Sawabe, M., Tanaka, N., Mochizuki, H., et al. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31818b4126 · Cited by 131 · see citing works
Regional Distribution of α-Synuclein Pathology in Unimpaired Aging and Alzheimer Disease
Parkkinen, L., Soininen, H. S., & Alafuzoff, I. I. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.4.363 · Cited by 129 · see citing works
Wakisaka, Y., Furuta, A., Tanizaki, Y., Kiyohara, Y., Iida, M., & Iwaki, T. (2003) · Acta Neuropathologica · doi:10.1007/s00401-003-0750-x · Cited by 128 · see citing works
Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease
Jicha, G. A., Schmitt, F. A., Abner, E., Nelson, P. T., Cooper, G. E., Smith, C. D., & Markesbery, W. R. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.09.017 · Cited by 111 · see citing works
Self-citationBrain Donation in Normal Aging
Schmitt, F. A., Wetherby, M. M. C., Wekstein, D. R., DEARTH, C., & Markesbery, W. R. (2001) · The Gerontologist · doi:10.1093/geront/41.6.716 · Cited by 88 · see citing works
Self-citationα‐Synuclein pathology is highly dependent on the case selection
Parkkinen, L., Soininen, H. S., Laakso, M., & Alafuzoff, I. I. (2001) · Neuropathology and Applied Neurobiology · doi:10.1046/j.0305-1846.2001.00342.x · Cited by 86 · see citing works
Lipkin, L. E. (1998) · PubMed · Cited by 76 · see citing works
Lewy bodies are not increased in progressive supranuclear palsy compared with normal controls
Tsuboi, Y., Ahlskog, J. E., Apaydın, H., Parisi, J. E., & Dickson, D. W. (2001) · Neurology · doi:10.1212/wnl.57.9.1675 · Cited by 48 · see citing works
Age-associated prevalence and risk factors of Lewy body pathology in a general population
Jellinger, K. A. (2003) · Acta Neuropathologica · doi:10.1007/s00401-003-0751-9 · Cited by 20 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [1]Giasson BI Lee VM Trojanowski JQ Esiri M Lee VM Trojanowski JQ Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy and the spectrum of diseases with alpha-synuclein inclusions The Neuropathology of Aging 2004 353 75 Cambridge University Press Cambridge
Cited by
Sorted by citations
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
Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria
Dickson, D. W., Braak, H., Duda, J. E., Duyckaerts, C., Gasser, T., Halliday, G. M., Hardy, J., Leverenz, J. B., Del Tredici, K., Wszolek, Z. K., et al. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70238-8 · Cited by 972 · see citing works
Bendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825 · see citing works
A timeline for Parkinson's disease
Hawkes, C. H., Del Tredici, K., & Braak, H. (2010) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2009.08.007 · Cited by 594 · see citing works
Analysis of Gut Microbiota in Patients with Parkinson’s Disease
Petrov, V. A., Saltykova, I. V., Zhukova, I. A., Alifirova, V. M., Zhukova, N. G., Dorofeeva, Y. B., Tyakht, A. V., Kovarsky, B. A., Alekseev, D. G., Kostryukova, E. S., et al. (2017) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-017-3700-7 · Cited by 487 · see citing works
α-synuclein in the pathophysiology of Alzheimer’s disease
Twohig, D., & Nielsen, H. M. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0320-x · Cited by 374 · see citing works
Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases
Espay, A. J., Vizcarra, J. A., Marsili, L., Lang, A. E., Simon, D. K., Merola, A., Josephs, K. A., Fasano, A., Morgante, F., Savica, R., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000006926 · Cited by 274 · 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
Ecology of the Aging Human Brain
Sonnen, J. A. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.157 · Cited by 174 · see citing works
Pathogenic Mechanisms of Neurodegeneration in Parkinson Disease
Mullin, S., & Schapira, A. H. V. (2015) · Neurologic Clinics · doi:10.1016/j.ncl.2014.09.010 · Cited by 108 · see citing works
Wennberg, A. M., Whitwell, J. L., Tosakulwong, N., Weigand, S. D., Murray, M. E., Machulda, M. M., Petrucelli, L., Mielke, M. M., Jack, C. R., Knopman, D. S., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.01.008 · Cited by 79 · see citing works
Preclinical 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-citationAkhtar, R. S., Licata, J. P., Luk, K. C., Shaw, L. M., Trojanowski, J. Q., & Lee, V. M. ‐. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14330 · Cited by 60 · see citing works
Staging 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
- Authors
- Markesbery, W. R., Jicha, G. A., Liu, H., & Schmitt, F. A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Markesbery, William R.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-07
- Volume
- 68
- Issue
- 7
- Pages
- 816-822
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC2704264
- OpenAlex
- W2005331929
- Cited by
- 210
- References
- 39
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 13 · 2023: 9 · 2022: 26 · 2021: 11 · 2020: 36 · 2019: 18 · 2018: 10 · 2017: 13 · 2016: 7 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 8
- FWCI
- 9.57
- 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)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Lewy bodies, Lewy neurites, incidental Lewy body disease, synucleinopathies, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, prevalence, medulla, amygdala, Braak stages, neurofibrillary tangles, neuritic plaques, Alzheimer's disease
- MeSH terms
- Aged, 80 and over, Brain, Cognition, Female, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Socioeconomic Factors, Lewy Bodies, Neurofibrillary Tangles, alpha-Synuclein, 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
