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Journal article
Lewy Bodies Contain Altered α-Synuclein in Brains of Many Familial Alzheimer’s Disease Patients with Mutations in Presenilin and Amyloid Precursor Protein Genes
The American journal of pathology, v 153(5), pp 1365-1370
01 Nov 1998
PMID: 9811326
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Abstract
Missense mutations in the α-synuclein gene cause familial Parkinson’s disease (PD), and α-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 α-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 α-, β-, and γ-synuclein. LBs were detected with α- but not β- or γ-synuclein antibodies in 22% of FAD brains, and α-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 α-synuclein-positive LBs, these inclusions may be more common in FAD brains than previously reported. Furthermore, α-synuclein antibodies decorated LB filaments by immunoelectron microscopy, and Western blots revealed that the solubility of α-synuclein was reduced compared with control brains. The presence of α-synuclein-positive LBs was not associated with any specific FAD mutation. These studies suggest that insoluble α-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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Details
- Title
- Lewy Bodies Contain Altered α-Synuclein in Brains of Many Familial Alzheimer’s Disease Patients with Mutations in Presenilin and Amyloid Precursor Protein Genes
- Creators
- Carol F. Lippa - Allegheny University of the Health SciencesHideo Fujiwara - University of TokyoDavid M.A. Mann - University of ManchesterBenoit Giasson - University of PennsylvaniaMinami Baba - University of TokyoMarie L. Schmidt - University of PennsylvaniaLinda E. Nee - National Institute of Neurological Disorders and StrokeBrendan O’ConnellDan A. Pollen - University of Massachusetts Medical SchoolPeter St. George-HyslopBernardino Ghetti - Indiana University – Purdue University IndianapolisDavid Nochlin - University of WashingtonThomas D. Bird - University of Washington Medical CenterNigel J. Cairns - Department of Neuropathology, Institute of Psychiatry, London, United KingdomVirginia M.-Y. Lee - University of PennsylvaniaTakeshi Iwatsubo - University of TokyoJohn Q. Trojanowski - University of Pennsylvania
- Publication Details
- The American journal of pathology, v 153(5), pp 1365-1370
- Publisher
- American Society for Investigative Pathology
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000076805100007
- Scopus ID
- 2-s2.0-18344417178
- Other Identifier
- 991019312359504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pathology