Dendritic spines provide cognitive resilience against Alzheimer's disease
Objective Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) begin years prior to clinical dementia onset. However, some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesize...
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| Veröffentlicht in: | Annals of neurology 2017-10, Vol.82 (4), p.602-614 |
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| container_title | Annals of neurology |
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| creator | Boros, Benjamin D. Greathouse, Kelsey M. Gentry, Erik G. Curtis, Kendall A. Birchall, Elizabeth L. Gearing, Marla Herskowitz, Jeremy H. |
| description | Objective
Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) begin years prior to clinical dementia onset. However, some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. We hypothesized that in cases with AD pathology, structural changes in dendritic spines would distinguish individuals who had or did not have clinical dementia.
Methods
We compared dendritic spines within layer II and III pyramidal neuron dendrites in Brodmann area 46 dorsolateral prefrontal cortex using the Golgi–Cox technique in 12 age‐matched pathology‐free controls, 8 controls with AD pathology (CAD), and 21 AD cases. We used highly optimized methods to trace impregnated dendrites from bright‐field microscopy images that enabled accurate 3‐dimensional digital reconstruction of dendritic structure for morphologic analyses.
Results
Spine density was similar among control and CAD cases but was reduced significantly in AD. Thin and mushroom spines were reduced significantly in AD compared to CAD brains, whereas stubby spine density was decreased significantly in CAD and AD compared to controls. Increased spine extent distinguished CAD cases from controls and AD. Linear regression analysis of all cases indicated that spine density was not associated with neuritic plaque score but did display negative correlation with Braak staging.
Interpretation
These observations provide cellular evidence to support the hypothesis that dendritic spine plasticity is a mechanism of cognitive resilience that protects older individuals with AD pathology from developing dementia. Ann Neurol 2017;82:602–614 |
| doi_str_mv | 10.1002/ana.25049 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5744899</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1940189775</sourcerecordid><originalsourceid>FETCH-LOGICAL-j4359-565a0b511835041822ca66ecac153c9fe6eab666f532a62f528ecbc8152dcfbf3</originalsourceid><addsrcrecordid>eNpdkU1LAzEQhoMoWqsH_4AseNDL2nx3cxGK3yB60XPIZmdrym52TdqK_nqj1aKeZph5eHlnXoQOCD4lGNOR8eaUCszVBhoQwUheUK420QAzyXNBGN9BuzHOMMZKEryNdmihKJGEDNDtBfgquLmzWeydh5j1oVu6CjLbTX2aLyELEF3jwFvIzNQ4H-fZpHl_BtdCOI5Z5SKYCHtoqzZNhP3vOkRPV5eP5zf53cP17fnkLp9xJlQupDC4FIQULDkmBaXWSAnW2OTcqhokmFJKWQtGjaS1oAXY0hZE0MrWZc2G6Gyl2y_KFioLfh5Mo_vgWhPedGec_rvx7llPu6UWY84LpZLAybdA6F4WEOe6ddFC0xgP3SJqojgmhRqPRUKP_qGzbhF8Oi9RQnBJGaWJOvztaG3l58sJGK2AV9fA23pPsP6MT6f49Fd8enI_-WrYB4cxjVc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1955462322</pqid></control><display><type>article</type><title>Dendritic spines provide cognitive resilience against Alzheimer's disease</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Boros, Benjamin D. ; Greathouse, Kelsey M. ; Gentry, Erik G. ; Curtis, Kendall A. ; Birchall, Elizabeth L. ; Gearing, Marla ; Herskowitz, Jeremy H.</creator><creatorcontrib>Boros, Benjamin D. ; Greathouse, Kelsey M. ; Gentry, Erik G. ; Curtis, Kendall A. ; Birchall, Elizabeth L. ; Gearing, Marla ; Herskowitz, Jeremy H.</creatorcontrib><description>Objective
Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) begin years prior to clinical dementia onset. However, some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. We hypothesized that in cases with AD pathology, structural changes in dendritic spines would distinguish individuals who had or did not have clinical dementia.
Methods
We compared dendritic spines within layer II and III pyramidal neuron dendrites in Brodmann area 46 dorsolateral prefrontal cortex using the Golgi–Cox technique in 12 age‐matched pathology‐free controls, 8 controls with AD pathology (CAD), and 21 AD cases. We used highly optimized methods to trace impregnated dendrites from bright‐field microscopy images that enabled accurate 3‐dimensional digital reconstruction of dendritic structure for morphologic analyses.
Results
Spine density was similar among control and CAD cases but was reduced significantly in AD. Thin and mushroom spines were reduced significantly in AD compared to CAD brains, whereas stubby spine density was decreased significantly in CAD and AD compared to controls. Increased spine extent distinguished CAD cases from controls and AD. Linear regression analysis of all cases indicated that spine density was not associated with neuritic plaque score but did display negative correlation with Braak staging.
Interpretation
These observations provide cellular evidence to support the hypothesis that dendritic spine plasticity is a mechanism of cognitive resilience that protects older individuals with AD pathology from developing dementia. Ann Neurol 2017;82:602–614</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.25049</identifier><identifier>PMID: 28921611</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Aged ; Aged, 80 and over ; Alzheimer Disease - pathology ; Alzheimer Disease - physiopathology ; Alzheimer's disease ; Analysis of Variance ; Biomarkers ; Brodmann's area ; Case-Control Studies ; Cognition - physiology ; Cognitive ability ; Dementia ; Dementia disorders ; Dendrites ; Dendritic plasticity ; Dendritic spines ; Dendritic Spines - pathology ; Dendritic Spines - ultrastructure ; Dendritic structure ; Density ; Digital imaging ; Female ; Golgi apparatus ; Hippocampus - pathology ; Hippocampus - ultrastructure ; Humans ; Image reconstruction ; Imaging, Three-Dimensional ; Linear Models ; Male ; Medical imaging ; Mental Status Schedule ; Microscopy ; Middle Aged ; Neurodegenerative diseases ; Neuroimaging ; Neurology ; Neurons - pathology ; Pathology ; Plastic foam ; Prefrontal cortex ; Regression analysis ; Resilience ; Silver Staining ; Spine</subject><ispartof>Annals of neurology, 2017-10, Vol.82 (4), p.602-614</ispartof><rights>2017 American Neurological Association</rights><rights>2017 American Neurological Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-7227-1470</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.25049$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.25049$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28921611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boros, Benjamin D.</creatorcontrib><creatorcontrib>Greathouse, Kelsey M.</creatorcontrib><creatorcontrib>Gentry, Erik G.</creatorcontrib><creatorcontrib>Curtis, Kendall A.</creatorcontrib><creatorcontrib>Birchall, Elizabeth L.</creatorcontrib><creatorcontrib>Gearing, Marla</creatorcontrib><creatorcontrib>Herskowitz, Jeremy H.</creatorcontrib><title>Dendritic spines provide cognitive resilience against Alzheimer's disease</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) begin years prior to clinical dementia onset. However, some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. We hypothesized that in cases with AD pathology, structural changes in dendritic spines would distinguish individuals who had or did not have clinical dementia.
Methods
We compared dendritic spines within layer II and III pyramidal neuron dendrites in Brodmann area 46 dorsolateral prefrontal cortex using the Golgi–Cox technique in 12 age‐matched pathology‐free controls, 8 controls with AD pathology (CAD), and 21 AD cases. We used highly optimized methods to trace impregnated dendrites from bright‐field microscopy images that enabled accurate 3‐dimensional digital reconstruction of dendritic structure for morphologic analyses.
Results
Spine density was similar among control and CAD cases but was reduced significantly in AD. Thin and mushroom spines were reduced significantly in AD compared to CAD brains, whereas stubby spine density was decreased significantly in CAD and AD compared to controls. Increased spine extent distinguished CAD cases from controls and AD. Linear regression analysis of all cases indicated that spine density was not associated with neuritic plaque score but did display negative correlation with Braak staging.
Interpretation
These observations provide cellular evidence to support the hypothesis that dendritic spine plasticity is a mechanism of cognitive resilience that protects older individuals with AD pathology from developing dementia. Ann Neurol 2017;82:602–614</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer Disease - physiopathology</subject><subject>Alzheimer's disease</subject><subject>Analysis of Variance</subject><subject>Biomarkers</subject><subject>Brodmann's area</subject><subject>Case-Control Studies</subject><subject>Cognition - physiology</subject><subject>Cognitive ability</subject><subject>Dementia</subject><subject>Dementia disorders</subject><subject>Dendrites</subject><subject>Dendritic plasticity</subject><subject>Dendritic spines</subject><subject>Dendritic Spines - pathology</subject><subject>Dendritic Spines - ultrastructure</subject><subject>Dendritic structure</subject><subject>Density</subject><subject>Digital imaging</subject><subject>Female</subject><subject>Golgi apparatus</subject><subject>Hippocampus - pathology</subject><subject>Hippocampus - ultrastructure</subject><subject>Humans</subject><subject>Image reconstruction</subject><subject>Imaging, Three-Dimensional</subject><subject>Linear Models</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Mental Status Schedule</subject><subject>Microscopy</subject><subject>Middle Aged</subject><subject>Neurodegenerative diseases</subject><subject>Neuroimaging</subject><subject>Neurology</subject><subject>Neurons - pathology</subject><subject>Pathology</subject><subject>Plastic foam</subject><subject>Prefrontal cortex</subject><subject>Regression analysis</subject><subject>Resilience</subject><subject>Silver Staining</subject><subject>Spine</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1LAzEQhoMoWqsH_4AseNDL2nx3cxGK3yB60XPIZmdrym52TdqK_nqj1aKeZph5eHlnXoQOCD4lGNOR8eaUCszVBhoQwUheUK420QAzyXNBGN9BuzHOMMZKEryNdmihKJGEDNDtBfgquLmzWeydh5j1oVu6CjLbTX2aLyELEF3jwFvIzNQ4H-fZpHl_BtdCOI5Z5SKYCHtoqzZNhP3vOkRPV5eP5zf53cP17fnkLp9xJlQupDC4FIQULDkmBaXWSAnW2OTcqhokmFJKWQtGjaS1oAXY0hZE0MrWZc2G6Gyl2y_KFioLfh5Mo_vgWhPedGec_rvx7llPu6UWY84LpZLAybdA6F4WEOe6ddFC0xgP3SJqojgmhRqPRUKP_qGzbhF8Oi9RQnBJGaWJOvztaG3l58sJGK2AV9fA23pPsP6MT6f49Fd8enI_-WrYB4cxjVc</recordid><startdate>201710</startdate><enddate>201710</enddate><creator>Boros, Benjamin D.</creator><creator>Greathouse, Kelsey M.</creator><creator>Gentry, Erik G.</creator><creator>Curtis, Kendall A.</creator><creator>Birchall, Elizabeth L.</creator><creator>Gearing, Marla</creator><creator>Herskowitz, Jeremy H.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7227-1470</orcidid></search><sort><creationdate>201710</creationdate><title>Dendritic spines provide cognitive resilience against Alzheimer's disease</title><author>Boros, Benjamin D. ; Greathouse, Kelsey M. ; Gentry, Erik G. ; Curtis, Kendall A. ; Birchall, Elizabeth L. ; Gearing, Marla ; Herskowitz, Jeremy H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j4359-565a0b511835041822ca66ecac153c9fe6eab666f532a62f528ecbc8152dcfbf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer Disease - physiopathology</topic><topic>Alzheimer's disease</topic><topic>Analysis of Variance</topic><topic>Biomarkers</topic><topic>Brodmann's area</topic><topic>Case-Control Studies</topic><topic>Cognition - physiology</topic><topic>Cognitive ability</topic><topic>Dementia</topic><topic>Dementia disorders</topic><topic>Dendrites</topic><topic>Dendritic plasticity</topic><topic>Dendritic spines</topic><topic>Dendritic Spines - pathology</topic><topic>Dendritic Spines - ultrastructure</topic><topic>Dendritic structure</topic><topic>Density</topic><topic>Digital imaging</topic><topic>Female</topic><topic>Golgi apparatus</topic><topic>Hippocampus - pathology</topic><topic>Hippocampus - ultrastructure</topic><topic>Humans</topic><topic>Image reconstruction</topic><topic>Imaging, Three-Dimensional</topic><topic>Linear Models</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Mental Status Schedule</topic><topic>Microscopy</topic><topic>Middle Aged</topic><topic>Neurodegenerative diseases</topic><topic>Neuroimaging</topic><topic>Neurology</topic><topic>Neurons - pathology</topic><topic>Pathology</topic><topic>Plastic foam</topic><topic>Prefrontal cortex</topic><topic>Regression analysis</topic><topic>Resilience</topic><topic>Silver Staining</topic><topic>Spine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Boros, Benjamin D.</creatorcontrib><creatorcontrib>Greathouse, Kelsey M.</creatorcontrib><creatorcontrib>Gentry, Erik G.</creatorcontrib><creatorcontrib>Curtis, Kendall A.</creatorcontrib><creatorcontrib>Birchall, Elizabeth L.</creatorcontrib><creatorcontrib>Gearing, Marla</creatorcontrib><creatorcontrib>Herskowitz, Jeremy H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Boros, Benjamin D.</au><au>Greathouse, Kelsey M.</au><au>Gentry, Erik G.</au><au>Curtis, Kendall A.</au><au>Birchall, Elizabeth L.</au><au>Gearing, Marla</au><au>Herskowitz, Jeremy H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dendritic spines provide cognitive resilience against Alzheimer's disease</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2017-10</date><risdate>2017</risdate><volume>82</volume><issue>4</issue><spage>602</spage><epage>614</epage><pages>602-614</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><abstract>Objective
Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) begin years prior to clinical dementia onset. However, some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. We hypothesized that in cases with AD pathology, structural changes in dendritic spines would distinguish individuals who had or did not have clinical dementia.
Methods
We compared dendritic spines within layer II and III pyramidal neuron dendrites in Brodmann area 46 dorsolateral prefrontal cortex using the Golgi–Cox technique in 12 age‐matched pathology‐free controls, 8 controls with AD pathology (CAD), and 21 AD cases. We used highly optimized methods to trace impregnated dendrites from bright‐field microscopy images that enabled accurate 3‐dimensional digital reconstruction of dendritic structure for morphologic analyses.
Results
Spine density was similar among control and CAD cases but was reduced significantly in AD. Thin and mushroom spines were reduced significantly in AD compared to CAD brains, whereas stubby spine density was decreased significantly in CAD and AD compared to controls. Increased spine extent distinguished CAD cases from controls and AD. Linear regression analysis of all cases indicated that spine density was not associated with neuritic plaque score but did display negative correlation with Braak staging.
Interpretation
These observations provide cellular evidence to support the hypothesis that dendritic spine plasticity is a mechanism of cognitive resilience that protects older individuals with AD pathology from developing dementia. Ann Neurol 2017;82:602–614</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28921611</pmid><doi>10.1002/ana.25049</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-7227-1470</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Aged Aged, 80 and over Alzheimer Disease - pathology Alzheimer Disease - physiopathology Alzheimer's disease Analysis of Variance Biomarkers Brodmann's area Case-Control Studies Cognition - physiology Cognitive ability Dementia Dementia disorders Dendrites Dendritic plasticity Dendritic spines Dendritic Spines - pathology Dendritic Spines - ultrastructure Dendritic structure Density Digital imaging Female Golgi apparatus Hippocampus - pathology Hippocampus - ultrastructure Humans Image reconstruction Imaging, Three-Dimensional Linear Models Male Medical imaging Mental Status Schedule Microscopy Middle Aged Neurodegenerative diseases Neuroimaging Neurology Neurons - pathology Pathology Plastic foam Prefrontal cortex Regression analysis Resilience Silver Staining Spine |
| title | Dendritic spines provide cognitive resilience against Alzheimer's disease |
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