Patterns and stages of α-synucleinopathy : Relevance in a population-based cohort
It is proposed that alpha-synucleinopathy (AS) initially affects the medulla oblongata and progresses to more rostral brain areas in a hierarchical sequence ("Braak hypothesis"). Predominant involvement of the amygdala is also described. This study examines the applicability of these patte...
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| Veröffentlicht in: | Neurology 2008-03, Vol.70 (13), p.1042-1048 |
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| description | It is proposed that alpha-synucleinopathy (AS) initially affects the medulla oblongata and progresses to more rostral brain areas in a hierarchical sequence ("Braak hypothesis"). Predominant involvement of the amygdala is also described. This study examines the applicability of these patterns, and their relationship to Alzheimer disease (AD) pathology, in brains of a population-based donor cohort.
Brains donated in two of six Cognitive Function and Ageing Study cohorts (Cambridgeshire and Nottingham) were examined. More than 80% were older than 80 years at death. The respondents were evaluated prospectively in life for cognitive decline and dementia. Immunocytochemistry for tau and alpha-synuclein was carried out in 208 brains to establish Braak stage and the pattern and severity of AS.
Seventy-six brains showed Lewy bodies. Half (51%) conformed to the Braak hypothesis while 17% had pathology in a higher region which was absent in a lower region. A further 29% showed amygdala-predominant pathology. Six brains showed predominant neocortical pathology with minimal pathology in amygdala or substantia nigra. The stage of AD pathology was not associated with particular patterns of AS.
alpha-Synucleinopathy (AS) is common in older people, and frequently associated with Alzheimer disease-type pathology. Although half of brains corresponded to the Braak hypothesis, and 29% to amygdala-predominant AS, there were a high proportion of cases which did not fit a staging system. An unexpectedly high proportion with a cortical form of Lewy body disease was identified. |
| doi_str_mv | 10.1212/01.wnl.0000306697.48738.b6 |
| format | Article |
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Brains donated in two of six Cognitive Function and Ageing Study cohorts (Cambridgeshire and Nottingham) were examined. More than 80% were older than 80 years at death. The respondents were evaluated prospectively in life for cognitive decline and dementia. Immunocytochemistry for tau and alpha-synuclein was carried out in 208 brains to establish Braak stage and the pattern and severity of AS.
Seventy-six brains showed Lewy bodies. Half (51%) conformed to the Braak hypothesis while 17% had pathology in a higher region which was absent in a lower region. A further 29% showed amygdala-predominant pathology. Six brains showed predominant neocortical pathology with minimal pathology in amygdala or substantia nigra. The stage of AD pathology was not associated with particular patterns of AS.
alpha-Synucleinopathy (AS) is common in older people, and frequently associated with Alzheimer disease-type pathology. Although half of brains corresponded to the Braak hypothesis, and 29% to amygdala-predominant AS, there were a high proportion of cases which did not fit a staging system. An unexpectedly high proportion with a cortical form of Lewy body disease was identified.</description><identifier>ISSN: 0028-3878</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/01.wnl.0000306697.48738.b6</identifier><identifier>PMID: 18362284</identifier><identifier>CODEN: NEURAI</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Aged ; Aged, 80 and over ; Aging - pathology ; alpha-Synuclein - analysis ; Alzheimer Disease - epidemiology ; Alzheimer Disease - pathology ; Amygdala - pathology ; Biological and medical sciences ; Biomarkers - analysis ; Brain - pathology ; Brain Stem - pathology ; Cohort Studies ; Development. Senescence. Regeneration. Transplantation ; Diagnosis, Differential ; Disease Progression ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Immunohistochemistry ; Lewy Bodies - pathology ; Lewy Body Disease - epidemiology ; Lewy Body Disease - pathology ; Longitudinal Studies ; Male ; Medical sciences ; Neurology ; Neurons - pathology ; Parkinson Disease - epidemiology ; Parkinson Disease - pathology ; Predictive Value of Tests ; Prospective Studies ; Registries ; tau Proteins - metabolism ; Tissue Donors ; United Kingdom - epidemiology ; Vertebrates: nervous system and sense organs</subject><ispartof>Neurology, 2008-03, Vol.70 (13), p.1042-1048</ispartof><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c321t-6c4e55ea1dbe31d9dfc56323d324b11af1e1eba896d8d727407ec4c32279b70f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20257432$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18362284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ZACCAI, J</creatorcontrib><creatorcontrib>BRAYNE, C</creatorcontrib><creatorcontrib>MCKEITH, I</creatorcontrib><creatorcontrib>MATTHEWS, F</creatorcontrib><creatorcontrib>INCE, P. G</creatorcontrib><creatorcontrib>MRC Cognitive Function, Ageing Neuropathology Study</creatorcontrib><title>Patterns and stages of α-synucleinopathy : Relevance in a population-based cohort</title><title>Neurology</title><addtitle>Neurology</addtitle><description>It is proposed that alpha-synucleinopathy (AS) initially affects the medulla oblongata and progresses to more rostral brain areas in a hierarchical sequence ("Braak hypothesis"). Predominant involvement of the amygdala is also described. This study examines the applicability of these patterns, and their relationship to Alzheimer disease (AD) pathology, in brains of a population-based donor cohort.
Brains donated in two of six Cognitive Function and Ageing Study cohorts (Cambridgeshire and Nottingham) were examined. More than 80% were older than 80 years at death. The respondents were evaluated prospectively in life for cognitive decline and dementia. Immunocytochemistry for tau and alpha-synuclein was carried out in 208 brains to establish Braak stage and the pattern and severity of AS.
Seventy-six brains showed Lewy bodies. Half (51%) conformed to the Braak hypothesis while 17% had pathology in a higher region which was absent in a lower region. A further 29% showed amygdala-predominant pathology. Six brains showed predominant neocortical pathology with minimal pathology in amygdala or substantia nigra. The stage of AD pathology was not associated with particular patterns of AS.
alpha-Synucleinopathy (AS) is common in older people, and frequently associated with Alzheimer disease-type pathology. Although half of brains corresponded to the Braak hypothesis, and 29% to amygdala-predominant AS, there were a high proportion of cases which did not fit a staging system. An unexpectedly high proportion with a cortical form of Lewy body disease was identified.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging - pathology</subject><subject>alpha-Synuclein - analysis</subject><subject>Alzheimer Disease - epidemiology</subject><subject>Alzheimer Disease - pathology</subject><subject>Amygdala - pathology</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - analysis</subject><subject>Brain - pathology</subject><subject>Brain Stem - pathology</subject><subject>Cohort Studies</subject><subject>Development. Senescence. Regeneration. Transplantation</subject><subject>Diagnosis, Differential</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Lewy Bodies - pathology</subject><subject>Lewy Body Disease - epidemiology</subject><subject>Lewy Body Disease - pathology</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Neurons - pathology</subject><subject>Parkinson Disease - epidemiology</subject><subject>Parkinson Disease - pathology</subject><subject>Predictive Value of Tests</subject><subject>Prospective Studies</subject><subject>Registries</subject><subject>tau Proteins - metabolism</subject><subject>Tissue Donors</subject><subject>United Kingdom - epidemiology</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0028-3878</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1O3TAQRq2qqFx-XgFZldpdUo-d2A47hChUQipCrcTOcuwJpMq1Q5xQ3cfqi_SZMHAFS2bjxZzP_nwI-QysBA78G4PybxhKlkcwKRtVVloJXbbyA1lBzWUhBb_5SFaMcV0IrfQu2UvpD2N5qZpPZBe0kJzrakWur-w84xQStcHTNNtbTDR29P-_Im3C4gbsQxztfLehx_QaB3ywwSHtA7V0jOMy2LmPoWhtQk9dvIvTfEB2OjskPNye--T397NfpxfF5c_zH6cnl4UTHOZCugrrGi34FgX4xneuzr2FF7xqAWwHCNha3UivveKqYgpdlbP5C61indgnX1_uHad4v2CazbpPDofBBoxLMopVQkkN74LQ1KqCRmfw-AV0U0xpws6MU7-208YAM0_qDQOT1Zs39eZZvWllDh9tX1naNfq36NZ1Br5sAZucHbopm-zTK8cZzzWygEcH2Y7Q</recordid><startdate>20080325</startdate><enddate>20080325</enddate><creator>ZACCAI, J</creator><creator>BRAYNE, C</creator><creator>MCKEITH, I</creator><creator>MATTHEWS, F</creator><creator>INCE, P. G</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20080325</creationdate><title>Patterns and stages of α-synucleinopathy : Relevance in a population-based cohort</title><author>ZACCAI, J ; BRAYNE, C ; MCKEITH, I ; MATTHEWS, F ; INCE, P. G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c321t-6c4e55ea1dbe31d9dfc56323d324b11af1e1eba896d8d727407ec4c32279b70f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging - pathology</topic><topic>alpha-Synuclein - analysis</topic><topic>Alzheimer Disease - epidemiology</topic><topic>Alzheimer Disease - pathology</topic><topic>Amygdala - pathology</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - analysis</topic><topic>Brain - pathology</topic><topic>Brain Stem - pathology</topic><topic>Cohort Studies</topic><topic>Development. Senescence. Regeneration. Transplantation</topic><topic>Diagnosis, Differential</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Lewy Bodies - pathology</topic><topic>Lewy Body Disease - epidemiology</topic><topic>Lewy Body Disease - pathology</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Neurons - pathology</topic><topic>Parkinson Disease - epidemiology</topic><topic>Parkinson Disease - pathology</topic><topic>Predictive Value of Tests</topic><topic>Prospective Studies</topic><topic>Registries</topic><topic>tau Proteins - metabolism</topic><topic>Tissue Donors</topic><topic>United Kingdom - epidemiology</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ZACCAI, J</creatorcontrib><creatorcontrib>BRAYNE, C</creatorcontrib><creatorcontrib>MCKEITH, I</creatorcontrib><creatorcontrib>MATTHEWS, F</creatorcontrib><creatorcontrib>INCE, P. G</creatorcontrib><creatorcontrib>MRC Cognitive Function, Ageing Neuropathology Study</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ZACCAI, J</au><au>BRAYNE, C</au><au>MCKEITH, I</au><au>MATTHEWS, F</au><au>INCE, P. G</au><aucorp>MRC Cognitive Function, Ageing Neuropathology Study</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Patterns and stages of α-synucleinopathy : Relevance in a population-based cohort</atitle><jtitle>Neurology</jtitle><addtitle>Neurology</addtitle><date>2008-03-25</date><risdate>2008</risdate><volume>70</volume><issue>13</issue><spage>1042</spage><epage>1048</epage><pages>1042-1048</pages><issn>0028-3878</issn><eissn>1526-632X</eissn><coden>NEURAI</coden><abstract>It is proposed that alpha-synucleinopathy (AS) initially affects the medulla oblongata and progresses to more rostral brain areas in a hierarchical sequence ("Braak hypothesis"). Predominant involvement of the amygdala is also described. This study examines the applicability of these patterns, and their relationship to Alzheimer disease (AD) pathology, in brains of a population-based donor cohort.
Brains donated in two of six Cognitive Function and Ageing Study cohorts (Cambridgeshire and Nottingham) were examined. More than 80% were older than 80 years at death. The respondents were evaluated prospectively in life for cognitive decline and dementia. Immunocytochemistry for tau and alpha-synuclein was carried out in 208 brains to establish Braak stage and the pattern and severity of AS.
Seventy-six brains showed Lewy bodies. Half (51%) conformed to the Braak hypothesis while 17% had pathology in a higher region which was absent in a lower region. A further 29% showed amygdala-predominant pathology. Six brains showed predominant neocortical pathology with minimal pathology in amygdala or substantia nigra. The stage of AD pathology was not associated with particular patterns of AS.
alpha-Synucleinopathy (AS) is common in older people, and frequently associated with Alzheimer disease-type pathology. Although half of brains corresponded to the Braak hypothesis, and 29% to amygdala-predominant AS, there were a high proportion of cases which did not fit a staging system. An unexpectedly high proportion with a cortical form of Lewy body disease was identified.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>18362284</pmid><doi>10.1212/01.wnl.0000306697.48738.b6</doi><tpages>7</tpages></addata></record> |
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| subjects | Aged Aged, 80 and over Aging - pathology alpha-Synuclein - analysis Alzheimer Disease - epidemiology Alzheimer Disease - pathology Amygdala - pathology Biological and medical sciences Biomarkers - analysis Brain - pathology Brain Stem - pathology Cohort Studies Development. Senescence. Regeneration. Transplantation Diagnosis, Differential Disease Progression Female Fundamental and applied biological sciences. Psychology Humans Immunohistochemistry Lewy Bodies - pathology Lewy Body Disease - epidemiology Lewy Body Disease - pathology Longitudinal Studies Male Medical sciences Neurology Neurons - pathology Parkinson Disease - epidemiology Parkinson Disease - pathology Predictive Value of Tests Prospective Studies Registries tau Proteins - metabolism Tissue Donors United Kingdom - epidemiology Vertebrates: nervous system and sense organs |
| title | Patterns and stages of α-synucleinopathy : Relevance in a population-based cohort |
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