Microglial activation and amyloid deposition in mild cognitive impairment : A PET study
Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI). To characterize in vivo with (11)C-(R)-PK11...
Gespeichert in:
| Veröffentlicht in: | Neurology 2009-01, Vol.72 (1), p.56-62 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 62 |
|---|---|
| container_issue | 1 |
| container_start_page | 56 |
| container_title | Neurology |
| container_volume | 72 |
| creator | OKELLO, A EDISON, P BROOKS, D. J ARCHER, H. A TURKHEIMER, F. E KENNEDY, J BULLOCK, R WALKER, Z KENNEDY, A FOX, N ROSSOR, M |
| description | Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI).
To characterize in vivo with (11)C-(R)-PK11195 and (11)C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI.
Fourteen subjects with MCI had (11)C-(R)-PK11195 and (11)C-PIB PET with psychometric tests.
Seven out of 14 (50%) patients with MCI had increased cortical (11)C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased (11)C-(R)-PK11195 uptake. The MCI subgroup with increased (11)C-PIB retention also showed increased cortical (11)C-(R)-PK11195 binding (p < 0.036) though this increase only remained significant in frontal cortex after a correction for multiple comparisons. There was no correlation between regional levels of (11)C-(R)-PK11195 and (11)C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased (11)C-(R)-PK11195 binding had increased levels of (11)C-PIB retention.
Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently. The detection of microglial activation in patients with MCI suggests that anti-inflammatory therapies may be relevant to the prevention of AD. |
| doi_str_mv | 10.1212/01.wnl.0000338622.27876.0d |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2817573</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>21220625</sourcerecordid><originalsourceid>FETCH-LOGICAL-c376t-5d57d9582bbcca245772c12fa6c9455c2979e700ad429251d10c802da46046793</originalsourceid><addsrcrecordid>eNqFkU1vEzEQhi0EoqHwF5CFRG-7jMdre7cHpKoqH1IRHIrgZjm2E4y8dlhvgvLvcdOohRNzGWnmmdfjeQl5xaBlyPANsPZ3ii3U4LyXiC2qXskW3COyYAJlIzl-f0wWANg3vFf9CXlWyk-A2lTDU3LCBoYInC3It0_BTnkdg4nU2DnszBxyoiY5asZ9zMFR5ze5hEM5JDqG6KjN61QrO0_DuDFhGn2a6Tm9oF-ubmiZt27_nDxZmVj8i2M-JV_fXd1cfmiuP7__eHlx3Viu5NwIJ5QbRI_LpbUGO6EUWoYrI-3QCWFxUINXAMZ1OKBgjoHtAZ3pJHRSDfyUvL3T3WyXo3e2LjKZqDdTGM2019kE_W8nhR96nXcae6aE4lXg7Cgw5V9bX2Y9hmJ9jCb5vC1ayvqeQPFfEG9PKg_g-R1YD1vK5Ff32zDQtwZqYLoaqB8M1AcDNbg6_PLv_zyMHh2rwOsjYIo1cTWZZEO555DBwIUA_gdlTqWA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>21220625</pqid></control><display><type>article</type><title>Microglial activation and amyloid deposition in mild cognitive impairment : A PET study</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><source>Alma/SFX Local Collection</source><creator>OKELLO, A ; EDISON, P ; BROOKS, D. J ; ARCHER, H. A ; TURKHEIMER, F. E ; KENNEDY, J ; BULLOCK, R ; WALKER, Z ; KENNEDY, A ; FOX, N ; ROSSOR, M</creator><creatorcontrib>OKELLO, A ; EDISON, P ; BROOKS, D. J ; ARCHER, H. A ; TURKHEIMER, F. E ; KENNEDY, J ; BULLOCK, R ; WALKER, Z ; KENNEDY, A ; FOX, N ; ROSSOR, M</creatorcontrib><description>Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI).
To characterize in vivo with (11)C-(R)-PK11195 and (11)C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI.
Fourteen subjects with MCI had (11)C-(R)-PK11195 and (11)C-PIB PET with psychometric tests.
Seven out of 14 (50%) patients with MCI had increased cortical (11)C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased (11)C-(R)-PK11195 uptake. The MCI subgroup with increased (11)C-PIB retention also showed increased cortical (11)C-(R)-PK11195 binding (p < 0.036) though this increase only remained significant in frontal cortex after a correction for multiple comparisons. There was no correlation between regional levels of (11)C-(R)-PK11195 and (11)C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased (11)C-(R)-PK11195 binding had increased levels of (11)C-PIB retention.
Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently. The detection of microglial activation in patients with MCI suggests that anti-inflammatory therapies may be relevant to the prevention of AD.</description><identifier>ISSN: 0028-3878</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/01.wnl.0000338622.27876.0d</identifier><identifier>PMID: 19122031</identifier><identifier>CODEN: NEURAI</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Aged ; Alzheimer Disease - complications ; Amyloid beta-Peptides - metabolism ; Benzothiazoles - metabolism ; Biological and medical sciences ; Brain Mapping ; Carbon Radioisotopes - metabolism ; Cognition Disorders - diagnosis ; Cognition Disorders - diagnostic imaging ; Cognition Disorders - etiology ; Cognition Disorders - pathology ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Female ; Follow-Up Studies ; Humans ; Isoquinolines - metabolism ; Magnetic Resonance Imaging ; Male ; Medical sciences ; Microglia - diagnostic imaging ; Microglia - metabolism ; Microglia - pathology ; Middle Aged ; Neurology ; Neuropsychological Tests ; Positron-Emission Tomography</subject><ispartof>Neurology, 2009-01, Vol.72 (1), p.56-62</ispartof><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009 by AAN Enterprises, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c376t-5d57d9582bbcca245772c12fa6c9455c2979e700ad429251d10c802da46046793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21093550$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19122031$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OKELLO, A</creatorcontrib><creatorcontrib>EDISON, P</creatorcontrib><creatorcontrib>BROOKS, D. J</creatorcontrib><creatorcontrib>ARCHER, H. A</creatorcontrib><creatorcontrib>TURKHEIMER, F. E</creatorcontrib><creatorcontrib>KENNEDY, J</creatorcontrib><creatorcontrib>BULLOCK, R</creatorcontrib><creatorcontrib>WALKER, Z</creatorcontrib><creatorcontrib>KENNEDY, A</creatorcontrib><creatorcontrib>FOX, N</creatorcontrib><creatorcontrib>ROSSOR, M</creatorcontrib><title>Microglial activation and amyloid deposition in mild cognitive impairment : A PET study</title><title>Neurology</title><addtitle>Neurology</addtitle><description>Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI).
To characterize in vivo with (11)C-(R)-PK11195 and (11)C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI.
Fourteen subjects with MCI had (11)C-(R)-PK11195 and (11)C-PIB PET with psychometric tests.
Seven out of 14 (50%) patients with MCI had increased cortical (11)C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased (11)C-(R)-PK11195 uptake. The MCI subgroup with increased (11)C-PIB retention also showed increased cortical (11)C-(R)-PK11195 binding (p < 0.036) though this increase only remained significant in frontal cortex after a correction for multiple comparisons. There was no correlation between regional levels of (11)C-(R)-PK11195 and (11)C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased (11)C-(R)-PK11195 binding had increased levels of (11)C-PIB retention.
Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently. The detection of microglial activation in patients with MCI suggests that anti-inflammatory therapies may be relevant to the prevention of AD.</description><subject>Aged</subject><subject>Alzheimer Disease - complications</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Benzothiazoles - metabolism</subject><subject>Biological and medical sciences</subject><subject>Brain Mapping</subject><subject>Carbon Radioisotopes - metabolism</subject><subject>Cognition Disorders - diagnosis</subject><subject>Cognition Disorders - diagnostic imaging</subject><subject>Cognition Disorders - etiology</subject><subject>Cognition Disorders - pathology</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Isoquinolines - metabolism</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microglia - diagnostic imaging</subject><subject>Microglia - metabolism</subject><subject>Microglia - pathology</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Neuropsychological Tests</subject><subject>Positron-Emission Tomography</subject><issn>0028-3878</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EoqHwF5CFRG-7jMdre7cHpKoqH1IRHIrgZjm2E4y8dlhvgvLvcdOohRNzGWnmmdfjeQl5xaBlyPANsPZ3ii3U4LyXiC2qXskW3COyYAJlIzl-f0wWANg3vFf9CXlWyk-A2lTDU3LCBoYInC3It0_BTnkdg4nU2DnszBxyoiY5asZ9zMFR5ze5hEM5JDqG6KjN61QrO0_DuDFhGn2a6Tm9oF-ubmiZt27_nDxZmVj8i2M-JV_fXd1cfmiuP7__eHlx3Viu5NwIJ5QbRI_LpbUGO6EUWoYrI-3QCWFxUINXAMZ1OKBgjoHtAZ3pJHRSDfyUvL3T3WyXo3e2LjKZqDdTGM2019kE_W8nhR96nXcae6aE4lXg7Cgw5V9bX2Y9hmJ9jCb5vC1ayvqeQPFfEG9PKg_g-R1YD1vK5Ff32zDQtwZqYLoaqB8M1AcDNbg6_PLv_zyMHh2rwOsjYIo1cTWZZEO555DBwIUA_gdlTqWA</recordid><startdate>20090106</startdate><enddate>20090106</enddate><creator>OKELLO, A</creator><creator>EDISON, P</creator><creator>BROOKS, D. J</creator><creator>ARCHER, H. A</creator><creator>TURKHEIMER, F. E</creator><creator>KENNEDY, J</creator><creator>BULLOCK, R</creator><creator>WALKER, Z</creator><creator>KENNEDY, A</creator><creator>FOX, N</creator><creator>ROSSOR, M</creator><general>Lippincott Williams & Wilkins</general><general>American Academy of Neurology</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><scope>5PM</scope></search><sort><creationdate>20090106</creationdate><title>Microglial activation and amyloid deposition in mild cognitive impairment : A PET study</title><author>OKELLO, A ; EDISON, P ; BROOKS, D. J ; ARCHER, H. A ; TURKHEIMER, F. E ; KENNEDY, J ; BULLOCK, R ; WALKER, Z ; KENNEDY, A ; FOX, N ; ROSSOR, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c376t-5d57d9582bbcca245772c12fa6c9455c2979e700ad429251d10c802da46046793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aged</topic><topic>Alzheimer Disease - complications</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Benzothiazoles - metabolism</topic><topic>Biological and medical sciences</topic><topic>Brain Mapping</topic><topic>Carbon Radioisotopes - metabolism</topic><topic>Cognition Disorders - diagnosis</topic><topic>Cognition Disorders - diagnostic imaging</topic><topic>Cognition Disorders - etiology</topic><topic>Cognition Disorders - pathology</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Isoquinolines - metabolism</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microglia - diagnostic imaging</topic><topic>Microglia - metabolism</topic><topic>Microglia - pathology</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Neuropsychological Tests</topic><topic>Positron-Emission Tomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OKELLO, A</creatorcontrib><creatorcontrib>EDISON, P</creatorcontrib><creatorcontrib>BROOKS, D. J</creatorcontrib><creatorcontrib>ARCHER, H. A</creatorcontrib><creatorcontrib>TURKHEIMER, F. E</creatorcontrib><creatorcontrib>KENNEDY, J</creatorcontrib><creatorcontrib>BULLOCK, R</creatorcontrib><creatorcontrib>WALKER, Z</creatorcontrib><creatorcontrib>KENNEDY, A</creatorcontrib><creatorcontrib>FOX, N</creatorcontrib><creatorcontrib>ROSSOR, M</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OKELLO, A</au><au>EDISON, P</au><au>BROOKS, D. J</au><au>ARCHER, H. A</au><au>TURKHEIMER, F. E</au><au>KENNEDY, J</au><au>BULLOCK, R</au><au>WALKER, Z</au><au>KENNEDY, A</au><au>FOX, N</au><au>ROSSOR, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microglial activation and amyloid deposition in mild cognitive impairment : A PET study</atitle><jtitle>Neurology</jtitle><addtitle>Neurology</addtitle><date>2009-01-06</date><risdate>2009</risdate><volume>72</volume><issue>1</issue><spage>56</spage><epage>62</epage><pages>56-62</pages><issn>0028-3878</issn><eissn>1526-632X</eissn><coden>NEURAI</coden><abstract>Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Abeta) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI).
To characterize in vivo with (11)C-(R)-PK11195 and (11)C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI.
Fourteen subjects with MCI had (11)C-(R)-PK11195 and (11)C-PIB PET with psychometric tests.
Seven out of 14 (50%) patients with MCI had increased cortical (11)C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased (11)C-(R)-PK11195 uptake. The MCI subgroup with increased (11)C-PIB retention also showed increased cortical (11)C-(R)-PK11195 binding (p < 0.036) though this increase only remained significant in frontal cortex after a correction for multiple comparisons. There was no correlation between regional levels of (11)C-(R)-PK11195 and (11)C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased (11)C-(R)-PK11195 binding had increased levels of (11)C-PIB retention.
Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently. The detection of microglial activation in patients with MCI suggests that anti-inflammatory therapies may be relevant to the prevention of AD.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>19122031</pmid><doi>10.1212/01.wnl.0000338622.27876.0d</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-3878 |
| ispartof | Neurology, 2009-01, Vol.72 (1), p.56-62 |
| issn | 0028-3878 1526-632X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2817573 |
| source | MEDLINE; Journals@Ovid Complete; Alma/SFX Local Collection |
| subjects | Aged Alzheimer Disease - complications Amyloid beta-Peptides - metabolism Benzothiazoles - metabolism Biological and medical sciences Brain Mapping Carbon Radioisotopes - metabolism Cognition Disorders - diagnosis Cognition Disorders - diagnostic imaging Cognition Disorders - etiology Cognition Disorders - pathology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Female Follow-Up Studies Humans Isoquinolines - metabolism Magnetic Resonance Imaging Male Medical sciences Microglia - diagnostic imaging Microglia - metabolism Microglia - pathology Middle Aged Neurology Neuropsychological Tests Positron-Emission Tomography |
| title | Microglial activation and amyloid deposition in mild cognitive impairment : A PET study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T05%3A55%3A12IST&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=Microglial%20activation%20and%20amyloid%20deposition%20in%20mild%20cognitive%20impairment%20:%20A%20PET%20study&rft.jtitle=Neurology&rft.au=OKELLO,%20A&rft.date=2009-01-06&rft.volume=72&rft.issue=1&rft.spage=56&rft.epage=62&rft.pages=56-62&rft.issn=0028-3878&rft.eissn=1526-632X&rft.coden=NEURAI&rft_id=info:doi/10.1212/01.wnl.0000338622.27876.0d&rft_dat=%3Cproquest_pubme%3E21220625%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=21220625&rft_id=info:pmid/19122031&rfr_iscdi=true |