White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
Background Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related...
Gespeichert in:
| Veröffentlicht in: | Neuropathology and applied neurobiology 2014-08, Vol.40 (5), p.591-602 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 602 |
|---|---|
| container_issue | 5 |
| container_start_page | 591 |
| container_title | Neuropathology and applied neurobiology |
| container_volume | 40 |
| creator | Craggs, Lucinda J. L. Yamamoto, Yumi Ihara, Masafumi Fenwick, Richard Burke, Matthew Oakley, Arthur E. Roeber, Sigrun Duering, Marco Kretzschmar, Hans Kalaria, Raj N. |
| description | Background
Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM.
Methods
We used post‐mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro‐caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles.
Results
The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P |
| doi_str_mv | 10.1111/nan.12073 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4282433</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1547856675</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5143-1f181faf5b460cba6aa3abe7c06c171427ce86595023f40146eb4abd233cb20e3</originalsourceid><addsrcrecordid>eNqNks9uEzEQxlcIREPgwAuglbi0h23t9b_NBSkKUIqiIEShiIvldWa7bnft1PZS8j48KE6TRoCEhC-2xr_5PN94suw5Rsc4rROr7DEukSAPshEmnBXlZIIeZiNEECtwRflB9iSEK4QQE3zyODsoSUWpEGyU_bxoTYS8VzGCz1cqtq5zl-tc2WW-NEE7a0FH42xubB5byBvvbFRd3rkaNjENHmqfAmqILrg-nZauN6mkmCufRI3bqK7zWxPbPAy1dj4anTBjG-V1DHdvdTBcO7AaVq3qdhmHs-nr6aez-dHT7FGjugDPdvs4-_z2zfnsXTH_cHo2m84LzTAlBW5whRvVsJpypGvFlSKqBqER11hgWgoNFWcThkrSUIQph5qqelkSousSARlnr7a6q6HuYanBxuRMrrzplV9Lp4z888aaVl6675KWVUkJSQKHOwHvbgYIUfaph9B1yoIbgsSMiopxLtj_oGU5EYzShL78C71yg7epExsKc0RxcjTOjraU9i4ED82-bozkZkxk-hN5NyaJffG70T15PxcJONkCt6aD9b-V5GK6uJcsthkmRPixz1D-WnJBBJMXi1P59cvH8_ffKiQp-QULdNnb</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1541604102</pqid></control><display><type>article</type><title>White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Craggs, Lucinda J. L. ; Yamamoto, Yumi ; Ihara, Masafumi ; Fenwick, Richard ; Burke, Matthew ; Oakley, Arthur E. ; Roeber, Sigrun ; Duering, Marco ; Kretzschmar, Hans ; Kalaria, Raj N.</creator><creatorcontrib>Craggs, Lucinda J. L. ; Yamamoto, Yumi ; Ihara, Masafumi ; Fenwick, Richard ; Burke, Matthew ; Oakley, Arthur E. ; Roeber, Sigrun ; Duering, Marco ; Kretzschmar, Hans ; Kalaria, Raj N.</creatorcontrib><description>Background
Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM.
Methods
We used post‐mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro‐caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles.
Results
The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P < 0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P < 0.01), with most prominent axonal abnormalities observed in the frontal WM (P < 0.05). The SIs of arterioles in CADASIL were increased by 25–45% throughout the regions assessed, with the highest change in the mid‐frontal region (P = 0.000).
Conclusions
Our results suggest disruption of either cortico‐cortical or subcortical‐cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures.</description><identifier>ISSN: 0305-1846</identifier><identifier>EISSN: 1365-2990</identifier><identifier>DOI: 10.1111/nan.12073</identifier><identifier>PMID: 23844775</identifier><identifier>CODEN: NANEDL</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Amyloid beta-Protein Precursor - metabolism ; Axons - metabolism ; Axons - pathology ; Brain ; Brain - metabolism ; Brain - pathology ; CADASIL ; CADASIL - metabolism ; CADASIL - pathology ; cognitive impairment ; disconnection ; Female ; Frontal Lobe - metabolism ; Frontal Lobe - pathology ; Humans ; Male ; Middle Aged ; Nerve Net - pathology ; Original ; Pathology ; stroke ; vascular dementia ; White Matter - blood supply ; White Matter - metabolism ; White Matter - pathology ; white matter changes</subject><ispartof>Neuropathology and applied neurobiology, 2014-08, Vol.40 (5), p.591-602</ispartof><rights>2013 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.</rights><rights>Copyright © 2014 British Neuropathological Society</rights><rights>2013 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5143-1f181faf5b460cba6aa3abe7c06c171427ce86595023f40146eb4abd233cb20e3</citedby><cites>FETCH-LOGICAL-c5143-1f181faf5b460cba6aa3abe7c06c171427ce86595023f40146eb4abd233cb20e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fnan.12073$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fnan.12073$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23844775$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Craggs, Lucinda J. L.</creatorcontrib><creatorcontrib>Yamamoto, Yumi</creatorcontrib><creatorcontrib>Ihara, Masafumi</creatorcontrib><creatorcontrib>Fenwick, Richard</creatorcontrib><creatorcontrib>Burke, Matthew</creatorcontrib><creatorcontrib>Oakley, Arthur E.</creatorcontrib><creatorcontrib>Roeber, Sigrun</creatorcontrib><creatorcontrib>Duering, Marco</creatorcontrib><creatorcontrib>Kretzschmar, Hans</creatorcontrib><creatorcontrib>Kalaria, Raj N.</creatorcontrib><title>White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)</title><title>Neuropathology and applied neurobiology</title><addtitle>Neuropathol Appl Neurobiol</addtitle><description>Background
Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM.
Methods
We used post‐mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro‐caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles.
Results
The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P < 0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P < 0.01), with most prominent axonal abnormalities observed in the frontal WM (P < 0.05). The SIs of arterioles in CADASIL were increased by 25–45% throughout the regions assessed, with the highest change in the mid‐frontal region (P = 0.000).
Conclusions
Our results suggest disruption of either cortico‐cortical or subcortical‐cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures.</description><subject>Adult</subject><subject>Aged</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Axons - metabolism</subject><subject>Axons - pathology</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>CADASIL</subject><subject>CADASIL - metabolism</subject><subject>CADASIL - pathology</subject><subject>cognitive impairment</subject><subject>disconnection</subject><subject>Female</subject><subject>Frontal Lobe - metabolism</subject><subject>Frontal Lobe - pathology</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nerve Net - pathology</subject><subject>Original</subject><subject>Pathology</subject><subject>stroke</subject><subject>vascular dementia</subject><subject>White Matter - blood supply</subject><subject>White Matter - metabolism</subject><subject>White Matter - pathology</subject><subject>white matter changes</subject><issn>0305-1846</issn><issn>1365-2990</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNqNks9uEzEQxlcIREPgwAuglbi0h23t9b_NBSkKUIqiIEShiIvldWa7bnft1PZS8j48KE6TRoCEhC-2xr_5PN94suw5Rsc4rROr7DEukSAPshEmnBXlZIIeZiNEECtwRflB9iSEK4QQE3zyODsoSUWpEGyU_bxoTYS8VzGCz1cqtq5zl-tc2WW-NEE7a0FH42xubB5byBvvbFRd3rkaNjENHmqfAmqILrg-nZauN6mkmCufRI3bqK7zWxPbPAy1dj4anTBjG-V1DHdvdTBcO7AaVq3qdhmHs-nr6aez-dHT7FGjugDPdvs4-_z2zfnsXTH_cHo2m84LzTAlBW5whRvVsJpypGvFlSKqBqER11hgWgoNFWcThkrSUIQph5qqelkSousSARlnr7a6q6HuYanBxuRMrrzplV9Lp4z888aaVl6675KWVUkJSQKHOwHvbgYIUfaph9B1yoIbgsSMiopxLtj_oGU5EYzShL78C71yg7epExsKc0RxcjTOjraU9i4ED82-bozkZkxk-hN5NyaJffG70T15PxcJONkCt6aD9b-V5GK6uJcsthkmRPixz1D-WnJBBJMXi1P59cvH8_ffKiQp-QULdNnb</recordid><startdate>201408</startdate><enddate>201408</enddate><creator>Craggs, Lucinda J. L.</creator><creator>Yamamoto, Yumi</creator><creator>Ihara, Masafumi</creator><creator>Fenwick, Richard</creator><creator>Burke, Matthew</creator><creator>Oakley, Arthur E.</creator><creator>Roeber, Sigrun</creator><creator>Duering, Marco</creator><creator>Kretzschmar, Hans</creator><creator>Kalaria, Raj N.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><general>BlackWell Publishing Ltd</general><scope>BSCLL</scope><scope>24P</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>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201408</creationdate><title>White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)</title><author>Craggs, Lucinda J. L. ; Yamamoto, Yumi ; Ihara, Masafumi ; Fenwick, Richard ; Burke, Matthew ; Oakley, Arthur E. ; Roeber, Sigrun ; Duering, Marco ; Kretzschmar, Hans ; Kalaria, Raj N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5143-1f181faf5b460cba6aa3abe7c06c171427ce86595023f40146eb4abd233cb20e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Axons - metabolism</topic><topic>Axons - pathology</topic><topic>Brain</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>CADASIL</topic><topic>CADASIL - metabolism</topic><topic>CADASIL - pathology</topic><topic>cognitive impairment</topic><topic>disconnection</topic><topic>Female</topic><topic>Frontal Lobe - metabolism</topic><topic>Frontal Lobe - pathology</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nerve Net - pathology</topic><topic>Original</topic><topic>Pathology</topic><topic>stroke</topic><topic>vascular dementia</topic><topic>White Matter - blood supply</topic><topic>White Matter - metabolism</topic><topic>White Matter - pathology</topic><topic>white matter changes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Craggs, Lucinda J. L.</creatorcontrib><creatorcontrib>Yamamoto, Yumi</creatorcontrib><creatorcontrib>Ihara, Masafumi</creatorcontrib><creatorcontrib>Fenwick, Richard</creatorcontrib><creatorcontrib>Burke, Matthew</creatorcontrib><creatorcontrib>Oakley, Arthur E.</creatorcontrib><creatorcontrib>Roeber, Sigrun</creatorcontrib><creatorcontrib>Duering, Marco</creatorcontrib><creatorcontrib>Kretzschmar, Hans</creatorcontrib><creatorcontrib>Kalaria, Raj N.</creatorcontrib><collection>Istex</collection><collection>Wiley-Blackwell Open Access Titles</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuropathology and applied neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Craggs, Lucinda J. L.</au><au>Yamamoto, Yumi</au><au>Ihara, Masafumi</au><au>Fenwick, Richard</au><au>Burke, Matthew</au><au>Oakley, Arthur E.</au><au>Roeber, Sigrun</au><au>Duering, Marco</au><au>Kretzschmar, Hans</au><au>Kalaria, Raj N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)</atitle><jtitle>Neuropathology and applied neurobiology</jtitle><addtitle>Neuropathol Appl Neurobiol</addtitle><date>2014-08</date><risdate>2014</risdate><volume>40</volume><issue>5</issue><spage>591</spage><epage>602</epage><pages>591-602</pages><issn>0305-1846</issn><eissn>1365-2990</eissn><coden>NANEDL</coden><abstract>Background
Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM.
Methods
We used post‐mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro‐caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles.
Results
The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P < 0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P < 0.01), with most prominent axonal abnormalities observed in the frontal WM (P < 0.05). The SIs of arterioles in CADASIL were increased by 25–45% throughout the regions assessed, with the highest change in the mid‐frontal region (P = 0.000).
Conclusions
Our results suggest disruption of either cortico‐cortical or subcortical‐cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23844775</pmid><doi>10.1111/nan.12073</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0305-1846 |
| ispartof | Neuropathology and applied neurobiology, 2014-08, Vol.40 (5), p.591-602 |
| issn | 0305-1846 1365-2990 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4282433 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Aged Amyloid beta-Protein Precursor - metabolism Axons - metabolism Axons - pathology Brain Brain - metabolism Brain - pathology CADASIL CADASIL - metabolism CADASIL - pathology cognitive impairment disconnection Female Frontal Lobe - metabolism Frontal Lobe - pathology Humans Male Middle Aged Nerve Net - pathology Original Pathology stroke vascular dementia White Matter - blood supply White Matter - metabolism White Matter - pathology white matter changes |
| title | White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T19%3A13%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=White%20matter%20pathology%20and%20disconnection%20in%20the%20frontal%20lobe%20in%20cerebral%20autosomal%20dominant%20arteriopathy%20with%20subcortical%20infarcts%20and%20leukoencephalopathy%20(CADASIL)&rft.jtitle=Neuropathology%20and%20applied%20neurobiology&rft.au=Craggs,%20Lucinda%20J.%20L.&rft.date=2014-08&rft.volume=40&rft.issue=5&rft.spage=591&rft.epage=602&rft.pages=591-602&rft.issn=0305-1846&rft.eissn=1365-2990&rft.coden=NANEDL&rft_id=info:doi/10.1111/nan.12073&rft_dat=%3Cproquest_pubme%3E1547856675%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1541604102&rft_id=info:pmid/23844775&rfr_iscdi=true |