The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index.
Lewy Bodies Contain Altered α-Synuclein in Brains of Many Familial Alzheimer's Disease Patients with Mutations in Presenilin and Amyloid Precursor Protein Genes
Open accessAbstract
Missense mutations in the alpha-synuclein gene cause familial Parkinson's disease (PD), and alpha-synuclein is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease (AD). To determine whether alpha-synuclein is a component of LBs in familial AD (FAD) patients with known mutations in presenilin (n = 65) or amyloid precursor protein (n = 9) genes, studies were conducted with antibodies to alpha-, beta-, and gamma-synuclein. LBs were detected with alpha- but not beta- or gamma-synuclein antibodies in 22% of FAD brains, and alpha-synuclein-positive LBs were most numerous in amygdala where some LBs co-localized with tau-positive neurofibrillary tangles. As 12 (63%) of 19 FAD amygdala samples contained alpha-synuclein-positive LBs, these inclusions may be more common in FAD brains than previously reported. Furthermore, alpha-synuclein antibodies decorated LB filaments by immunoelectron microscopy, and Western blots revealed that the solubility of alpha-synuclein was reduced compared with control brains. The presence of alpha-synuclein-positive LBs was not associated with any specific FAD mutation. These studies suggest that insoluble alpha-synuclein aggregates into filaments that form LBs in many FAD patients, and we speculate that these inclusions may compromise the function and/or viability of affected neurons in the FAD brain.
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“two studies have shown that individuals with PSEN1 mutations have increased, yet heterogeneous limbic LRP [22, 25].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [22]
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“co-morbid αSyn pathology has been reported in more than half of all autopsy-confirmed AD cases [22–24]”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [22]
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“co-morbid αSyn pathology has been reported in more than half of all autopsy-confirmed AD cases [22–24]”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [22]
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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
Self-citationDiagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium
McKeith, I. G., Boeve, B. F., Dickson, D. W., Halliday, G., Taylor, J.-P., Weintraub, D., Aarsland, D., Galvin, J., Attems, J., Ballard, C. G., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004058 · Cited by 4,476
Self-citationInflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345
Alpha-synuclein and neurodegenerative diseases
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Metadata
- Authors
- 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., Ghetti, B., Nochlin, D., Bird, T. D., Cairns, N. J., Lee, V. M.-Y., Iwatsubo, T., & Trojanowski, J. Q.
- Affiliations
- The University of Tokyo (JP)
- University of Manchester (GB)
- University of Pennsylvania (US)
- National Institute of Neurological Disorders and Stroke (US)
- University of Massachusetts Chan Medical School (US)
- Indiana University Hospital (US)
- University of Washington (US)
- Corresponding author
- Lippa, Carol F.
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 1998-11
- Volume
- 153
- Issue
- 5
- Pages
- 1365-1370
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1853391
- OpenAlex
- W2066155243
- Cited by
- 533
- References
- 35
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 23 · 2023: 16 · 2022: 19 · 2021: 21 · 2020: 19 · 2019: 17 · 2018: 16 · 2017: 9 · 2016: 11 · 2015: 13 · 2014: 25 · 2013: 13 · 2012: 11
- FWCI
- 17.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r29ag013623-06)
- National Institute on Aging (P30AG010133, AG09215, U01AG006781, AG13623, P30AG010124, P01AG009215, AG-10124, P50AG005136)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Lewy bodies, alpha-synuclein, familial Alzheimer's disease, presenilin mutations, amyloid precursor protein mutations, amygdala, alpha-synuclein aggregation, protein insolubility, immunoelectron microscopy
- MeSH terms
- Adult, Aged, Alzheimer Disease, Brain, Female, Humans, Immunohistochemistry, Male, Membrane Proteins, Middle Aged, Mutation, Nerve Tissue Proteins, Blotting, Western, Microscopy, Immunoelectron, Amyloid beta-Protein Precursor, Lewy Bodies, Synucleins, alpha-Synuclein, gamma-Synuclein, Presenilin-1
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