Lewy bodies contain altered α-synuclein in brains of many familial Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes
Identifieur interne : 003A33 ( Main/Exploration ); précédent : 003A32; suivant : 003A34Lewy bodies contain altered α-synuclein in brains of many familial Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes
Auteurs : C. F. Lippa [États-Unis] ; H. Fujiwara [Japon] ; D. M. A. Mann [Royaume-Uni] ; B. Giasson [États-Unis] ; M. Baba [Japon] ; M. L. Schmidt [États-Unis] ; L. E. Nee [États-Unis] ; B. O'Connell [États-Unis] ; D. A. Pollen [États-Unis] ; P. S. George-Hyslop [Canada] ; B. Ghetti [États-Unis] ; D. Nochlin [États-Unis] ; T. D. Bird [États-Unis] ; N. J. Cairns [Royaume-Uni] ; V. M.-Y. Lee [États-Unis] ; T. Iwatsubo [Japon] ; J. Q. Trojanowski [États-Unis]Source :
- The American journal of pathology [ 0002-9440 ] ; 1998.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
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.
Affiliations:
- Canada, Japon, Royaume-Uni, États-Unis
- Angleterre, Grand Londres, Grand Manchester, Indiana, Maryland, Massachusetts, Ontario, Pennsylvanie, Washington (État)
- Londres, Manchester, Tokyo, Toronto
- Université de Toronto
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Lewy bodies contain altered α-synuclein in brains of many familial Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes</title><author><name sortKey="Lippa, C F" sort="Lippa, C F" uniqKey="Lippa C" first="C. F." last="Lippa">C. F. Lippa</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Allegheny University of the Health Sciences MCP Division</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Fujiwara, H" sort="Fujiwara, H" uniqKey="Fujiwara H" first="H." last="Fujiwara">H. Fujiwara</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neuropathology and Neuroscience, University of Tokyo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement></placeName></affiliation></author><author><name sortKey="Mann, D M A" sort="Mann, D M A" uniqKey="Mann D" first="D. M. A." last="Mann">D. M. A. Mann</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Pathologic Sciences, Manchester University</s1><s2>Manchester</s2><s3>GBR</s3><sZ>3 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Giasson, B" sort="Giasson, B" uniqKey="Giasson B" first="B." last="Giasson">B. Giasson</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>15 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Baba, M" sort="Baba, M" uniqKey="Baba M" first="M." last="Baba">M. Baba</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neuropathology and Neuroscience, University of Tokyo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement></placeName></affiliation></author><author><name sortKey="Schmidt, M L" sort="Schmidt, M L" uniqKey="Schmidt M" first="M. L." last="Schmidt">M. L. Schmidt</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>15 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Nee, L E" sort="Nee, L E" uniqKey="Nee L" first="L. E." last="Nee">L. E. Nee</name><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Family Studies Unit, National Institute of Neurological Disorders and Stroke, Clinical Center</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="O Connell, B" sort="O Connell, B" uniqKey="O Connell B" first="B." last="O'Connell">B. O'Connell</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Allegheny University of the Health Sciences MCP Division</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Pollen, D A" sort="Pollen, D A" uniqKey="Pollen D" first="D. A." last="Pollen">D. A. Pollen</name><affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Department of Neurology, University of Massachusetts Medical Center</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="George Hyslop, P S" sort="George Hyslop, P S" uniqKey="George Hyslop P" first="P. S." last="George-Hyslop">P. S. George-Hyslop</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Departments of Medicine (Neurology) and Medical Biophysics, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Ghetti, B" sort="Ghetti, B" uniqKey="Ghetti B" first="B." last="Ghetti">B. Ghetti</name><affiliation wicri:level="2"><inist:fA14 i1="08"><s1>Department of Pathology Indiana University Medical Center</s1><s2>Indianapolis, Indiana</s2><s3>USA</s3><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Nochlin, D" sort="Nochlin, D" uniqKey="Nochlin D" first="D." last="Nochlin">D. Nochlin</name><affiliation wicri:level="2"><inist:fA14 i1="09"><s1>Department of Pathology, University of Washington School of Medicine</s1><s2>Seattle, Washington</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Bird, T D" sort="Bird, T D" uniqKey="Bird T" first="T. D." last="Bird">T. D. Bird</name><affiliation wicri:level="2"><inist:fA14 i1="10"><s1>Department of Neurology, VA Medical Center and University of Washington School of Medicine</s1><s2>Seattle, Washington</s2><s3>USA</s3><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Cairns, N J" sort="Cairns, N J" uniqKey="Cairns N" first="N. J." last="Cairns">N. J. Cairns</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Department of Neuropathology, Institute of Psychiatry</s1><s2>London</s2><s3>GBR</s3><sZ>14 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Lee, V M Y" sort="Lee, V M Y" uniqKey="Lee V" first="V. M.-Y." last="Lee">V. M.-Y. Lee</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>15 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Iwatsubo, T" sort="Iwatsubo, T" uniqKey="Iwatsubo T" first="T." last="Iwatsubo">T. Iwatsubo</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neuropathology and Neuroscience, University of Tokyo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement></placeName></affiliation></author><author><name sortKey="Trojanowski, J Q" sort="Trojanowski, J Q" uniqKey="Trojanowski J" first="J. Q." last="Trojanowski">J. Q. Trojanowski</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>15 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">99-0012433</idno><date when="1998">1998</date><idno type="stanalyst">PASCAL 99-0012433 INIST</idno><idno type="RBID">Pascal:99-0012433</idno><idno type="wicri:Area/PascalFrancis/Corpus">000D94</idno><idno type="wicri:Area/PascalFrancis/Curation">001129</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000D04</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000D04</idno><idno type="wicri:doubleKey">0002-9440:1998:Lippa C:lewy:bodies:contain</idno><idno type="wicri:Area/Main/Merge">004054</idno><idno type="wicri:Area/Main/Curation">003A33</idno><idno type="wicri:Area/Main/Exploration">003A33</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Lewy bodies contain altered α-synuclein in brains of many familial Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes</title><author><name sortKey="Lippa, C F" sort="Lippa, C F" uniqKey="Lippa C" first="C. F." last="Lippa">C. F. Lippa</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Allegheny University of the Health Sciences MCP Division</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Fujiwara, H" sort="Fujiwara, H" uniqKey="Fujiwara H" first="H." last="Fujiwara">H. Fujiwara</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neuropathology and Neuroscience, University of Tokyo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement></placeName></affiliation></author><author><name sortKey="Mann, D M A" sort="Mann, D M A" uniqKey="Mann D" first="D. M. A." last="Mann">D. M. A. Mann</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Pathologic Sciences, Manchester University</s1><s2>Manchester</s2><s3>GBR</s3><sZ>3 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Giasson, B" sort="Giasson, B" uniqKey="Giasson B" first="B." last="Giasson">B. Giasson</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>15 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Baba, M" sort="Baba, M" uniqKey="Baba M" first="M." last="Baba">M. Baba</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neuropathology and Neuroscience, University of Tokyo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement></placeName></affiliation></author><author><name sortKey="Schmidt, M L" sort="Schmidt, M L" uniqKey="Schmidt M" first="M. L." last="Schmidt">M. L. Schmidt</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>15 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Nee, L E" sort="Nee, L E" uniqKey="Nee L" first="L. E." last="Nee">L. E. Nee</name><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Family Studies Unit, National Institute of Neurological Disorders and Stroke, Clinical Center</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="O Connell, B" sort="O Connell, B" uniqKey="O Connell B" first="B." last="O'Connell">B. O'Connell</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Neurology, Allegheny University of the Health Sciences MCP Division</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Pollen, D A" sort="Pollen, D A" uniqKey="Pollen D" first="D. A." last="Pollen">D. A. Pollen</name><affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Department of Neurology, University of Massachusetts Medical Center</s1><s2>Worcester, Massachusetts</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="George Hyslop, P S" sort="George Hyslop, P S" uniqKey="George Hyslop P" first="P. S." last="George-Hyslop">P. S. George-Hyslop</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Departments of Medicine (Neurology) and Medical Biophysics, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Ghetti, B" sort="Ghetti, B" uniqKey="Ghetti B" first="B." last="Ghetti">B. Ghetti</name><affiliation wicri:level="2"><inist:fA14 i1="08"><s1>Department of Pathology Indiana University Medical Center</s1><s2>Indianapolis, Indiana</s2><s3>USA</s3><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Nochlin, D" sort="Nochlin, D" uniqKey="Nochlin D" first="D." last="Nochlin">D. Nochlin</name><affiliation wicri:level="2"><inist:fA14 i1="09"><s1>Department of Pathology, University of Washington School of Medicine</s1><s2>Seattle, Washington</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Bird, T D" sort="Bird, T D" uniqKey="Bird T" first="T. D." last="Bird">T. D. Bird</name><affiliation wicri:level="2"><inist:fA14 i1="10"><s1>Department of Neurology, VA Medical Center and University of Washington School of Medicine</s1><s2>Seattle, Washington</s2><s3>USA</s3><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Cairns, N J" sort="Cairns, N J" uniqKey="Cairns N" first="N. J." last="Cairns">N. J. Cairns</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Department of Neuropathology, Institute of Psychiatry</s1><s2>London</s2><s3>GBR</s3><sZ>14 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Lee, V M Y" sort="Lee, V M Y" uniqKey="Lee V" first="V. M.-Y." last="Lee">V. M.-Y. Lee</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>15 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Iwatsubo, T" sort="Iwatsubo, T" uniqKey="Iwatsubo T" first="T." last="Iwatsubo">T. Iwatsubo</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neuropathology and Neuroscience, University of Tokyo</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement></placeName></affiliation></author><author><name sortKey="Trojanowski, J Q" sort="Trojanowski, J Q" uniqKey="Trojanowski J" first="J. Q." last="Trojanowski">J. Q. Trojanowski</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>15 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></analytic><series><title level="j" type="main">The American journal of pathology</title><title level="j" type="abbreviated">Am. j. pathol.</title><idno type="ISSN">0002-9440</idno><imprint><date when="1998">1998</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">The American journal of pathology</title><title level="j" type="abbreviated">Am. j. pathol.</title><idno type="ISSN">0002-9440</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alzheimer disease</term><term>Amyloid precursor protein</term><term>Electron microscopy</term><term>Familial form</term><term>Gene</term><term>Genetic disease</term><term>Human</term><term>Immunoblotting assay</term><term>Immunohistochemistry</term><term>Lewy body</term><term>Mutation</term><term>Pathogenesis</term><term>Presenilin</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Démence Alzheimer</term><term>Maladie héréditaire</term><term>Immunohistochimie</term><term>Microscopie électronique</term><term>Méthode immunoblotting</term><term>Corps Lewy</term><term>Mutation</term><term>Gène</term><term>Préséniline</term><term>Protéine précurseur amyloïde</term><term>Pathogénie</term><term>Homme</term><term>α-Synuclein</term><term>Forme familiale</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Japon</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Grand Manchester</li><li>Indiana</li><li>Maryland</li><li>Massachusetts</li><li>Ontario</li><li>Pennsylvanie</li><li>Washington (État)</li></region><settlement><li>Londres</li><li>Manchester</li><li>Tokyo</li><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Lippa, C F" sort="Lippa, C F" uniqKey="Lippa C" first="C. F." last="Lippa">C. F. Lippa</name></region><name sortKey="Bird, T D" sort="Bird, T D" uniqKey="Bird T" first="T. D." last="Bird">T. D. Bird</name><name sortKey="Ghetti, B" sort="Ghetti, B" uniqKey="Ghetti B" first="B." last="Ghetti">B. Ghetti</name><name sortKey="Giasson, B" sort="Giasson, B" uniqKey="Giasson B" first="B." last="Giasson">B. Giasson</name><name sortKey="Lee, V M Y" sort="Lee, V M Y" uniqKey="Lee V" first="V. M.-Y." last="Lee">V. M.-Y. Lee</name><name sortKey="Nee, L E" sort="Nee, L E" uniqKey="Nee L" first="L. E." last="Nee">L. E. Nee</name><name sortKey="Nochlin, D" sort="Nochlin, D" uniqKey="Nochlin D" first="D." last="Nochlin">D. Nochlin</name><name sortKey="O Connell, B" sort="O Connell, B" uniqKey="O Connell B" first="B." last="O'Connell">B. O'Connell</name><name sortKey="Pollen, D A" sort="Pollen, D A" uniqKey="Pollen D" first="D. A." last="Pollen">D. A. Pollen</name><name sortKey="Schmidt, M L" sort="Schmidt, M L" uniqKey="Schmidt M" first="M. L." last="Schmidt">M. L. Schmidt</name><name sortKey="Trojanowski, J Q" sort="Trojanowski, J Q" uniqKey="Trojanowski J" first="J. Q." last="Trojanowski">J. Q. Trojanowski</name></country><country name="Japon"><noRegion><name sortKey="Fujiwara, H" sort="Fujiwara, H" uniqKey="Fujiwara H" first="H." last="Fujiwara">H. Fujiwara</name></noRegion><name sortKey="Baba, M" sort="Baba, M" uniqKey="Baba M" first="M." last="Baba">M. Baba</name><name sortKey="Iwatsubo, T" sort="Iwatsubo, T" uniqKey="Iwatsubo T" first="T." last="Iwatsubo">T. Iwatsubo</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Mann, D M A" sort="Mann, D M A" uniqKey="Mann D" first="D. M. A." last="Mann">D. M. A. Mann</name></region><name sortKey="Cairns, N J" sort="Cairns, N J" uniqKey="Cairns N" first="N. J." last="Cairns">N. J. Cairns</name></country><country name="Canada"><region name="Ontario"><name sortKey="George Hyslop, P S" sort="George Hyslop, P S" uniqKey="George Hyslop P" first="P. S." last="George-Hyslop">P. S. 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