Lewy Body-Related α-Synucleinopathy in Aging
Abstract
To clarify the significance of Lewy body (LB)-related alpha-synucleinopathy in aging, we investigated the incidence of LBs in 1,241 consecutive autopsy cases (663 males and 578 females). LB pathology was identified histologically in sections stained with hematoxylin and eosin and with anti-ubiquitin and anti-alpha-synuclein antibodies. Cases without LBs were classified as LB stage 0 (987 cases). Cases with LBs were classified as follows: LB stage I = incidental LBs (149 cases); LB stage II = LB-related degeneration without attributable clinical symptoms (47 cases); LB stage III = Parkinson disease without dementia (10 cases); LB stage IV = dementia with Lewy bodies (DLB) transitional (limbic) form (25 cases); and LB stage V = DLB neocortical form (23 cases). The average age at death was greater for those cases with LBs. There were no gender differences in the LB pathology. G842A polymorphism in the paraoxonase I gene was associated with men in LB stage II or above and suggests a gender-specific risk factor. LB stage V had higher stages of neurofibrillary tangle and senile plaque involvement and also had a higher frequency of apolipoprotein E epsilon4. Our findings indicate that LBs are associated with cognitive decline, either independently or synergistically with neurofibrillary tangles and senile plaques.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
LBD has been observed in individuals without apparent cognitive or motor deficit, though much less common than AD neuropathologic change.
“Clinico-pathologic correlation for individuals without cognitive impairment should indicate that, although much less common than AD neuropathologic change, LBD has been observed in individuals without apparent cognitive or motor deficit [1,49]; this may represent pre-clinical LBD [12,22,31].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [49]
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
Flagged first, then by citations
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
Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,992 · see citing works
Goedert, M., Spillantini, M. G., Del Tredici, K., & Braak, H. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.242 · Cited by 1,190 · see citing works
Parkinson's disease: a dual‐hit hypothesis
Hawkes, C. H., Del Tredici, K., & Braak, H. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00874.x · Cited by 1,021 · see citing works
Braak, H., Bohl, J. R., Müller, C. M., Rüb, U., de Vos, R. A. I., & Del Tredici, K. (2006) · Movement Disorders · doi:10.1002/mds.21065 · Cited by 630 · see citing works
Essential tremor — Neurodegenerative or nondegenerative disease towards a working definition of ET
Deuschl, G., & Elble, R. (2009) · Movement Disorders · doi:10.1002/mds.22755 · Cited by 232 · see citing works
Incidence and extent of TDP-43 accumulation in aging human brain
Uchino, A., Takao, M., Hatsuta, H., Sumikura, H., Nakano, Y., Nogami, A., Saito, Y., Arai, T., Nishiyama, K., & Murayama, S. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0215-1 · Cited by 144 · see citing works
Self-citationReduced striatal tyrosine hydroxylase in incidental Lewy body disease
Beach, T. G., Adler, C. H., Sue, L. I., Peirce, J. B., Bachalakuri, J., Dalsing-Hernandez, J. E., Lue, L. F., Caviness, J. N., Connor, D. J., Sabbagh, M. N., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-007-0313-7 · Cited by 128 · see citing works
Neuropathology of mild cognitive impairment
Saito, Y., & Murayama, S. (2007) · Neuropathology · doi:10.1111/j.1440-1789.2007.00806.x · Cited by 92 · see citing works
Self-citationVulnerability of mesostriatal dopaminergic neurons in Parkinson’s disease
González-Hernández, T. (2010) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2010.00140 · Cited by 65 · see citing works
Elble, R. J., & Deuschl, G. (2009) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-009-0041-6 · Cited by 52 · see citing works
- Authors
- Saito, Y., Ruberu, N. N., Sawabe, M., Arai, T., Kazama, H., Hosoi, T., Yamanouchi, H., & Murayama, S.
- Affiliations
- Tokyo Metropolitan Institute of Gerontology (JP)
- Tokyo Metropolitan Geriatric Hospital (JP)
- Corresponding author
- Murayama, Shigeo
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07
- Volume
- 63
- Issue
- 7
- Pages
- 742-749
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2343262276
- Cited by
- 200
- References
- 1
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 1 · 2022: 11 · 2021: 6 · 2020: 28 · 2019: 2 · 2018: 2 · 2017: 10 · 2016: 6 · 2015: 9 · 2014: 8 · 2013: 5 · 2012: 11
- FWCI
- 7.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Lewy bodies, synucleinopathies, aging, dementia with Lewy bodies, Parkinson's disease, APOE ε4, neurofibrillary tangles, amyloid plaques, cognitive decline, age at death, sex differences
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Aging, Apolipoproteins E, Brain, Cerebral Cortex, Female, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Tissue Proteins, Parkinson Disease, Risk Factors, Sex Factors, Lewy Bodies, Neurofibrillary Tangles, Disease Progression, Genetic Predisposition to Disease, Lewy Body Disease, Ubiquitin, Aryldialkylphosphatase, Synucleins, Apolipoprotein E4, 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
