Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment
INTRODUCTION Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD). METHODS Ten cognitivel...
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| Veröffentlicht in: | Alzheimer's & dementia 2024-06, Vol.20 (6), p.3876-3888 |
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| creator | Wang, Jie Huang, Qi He, Kun Li, Junpeng Guo, Tengfei Yang, Yang Lin, Zengping Li, Songye Vanderlinden, Greet Huang, Yiyun Van Laere, Koen Guan, Yihui Guo, Qihao Ni, Ruiqing Li, Binying Xie, Fang |
| description | INTRODUCTION
Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD).
METHODS
Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT‐1 and [18F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition.
RESULTS
CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition.
CONCLUSIONS
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked.
Highlights
Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs.
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD.
Regional synaptic density was closely associated with regional mGluR5 availability.
mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition.
With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD. |
| doi_str_mv | 10.1002/alz.13817 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11180932</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3041231521</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4167-1267a28331eee44048fd7fa4a98acc2bebee735e5bdfd892c7f91f8a6114f6d63</originalsourceid><addsrcrecordid>eNp1kctuEzEUhkcIREthwQsgL-kirW9zW6GoKlApEpUoLNhYZ-wziZFnPNhOquH5eDBc0kZ00Y2PLX_-fkt_Ubxl9IxRys_B_T5jomH1s-KYlSVflLxunx_2FT0qXsX4k1JJG1a-LI5EUwkphDwu_lwHjPMIU7KaGByjTXOeCcNgRzSkm8nX73xJri9viI1EOx_RzQRi9NpCysStTRsy-ZgOmgETdD4FP-XD2m0TDJkkATVOyQdSEtiBddBZd5cGoyF2NDhhXsZEfE9gmJ23hkyQNt759ZwBghBysvbr0Sa7Q2KHCWwY8pPXxYseXMQ39_Ok-Pbx8ubi82L15dPVxXK10JJV9YLxqgbeCMEQUUoqm97UPUhoG9Cad9gh1qLEsjO9aVqu675lfQMVY7KvTCVOig9777TtBjQ6Rwdwagp2gDArD1Y9vhntRq39TjHGGtoKng3v7w3B_9piTGqwUaNzMKLfRiWoZFywkrOMnu5RHXyMAftDDqPqrnaVa1f_as_su_8_diAfes7A-R64tQ7np01qufqxV_4Fz-y-1w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3041231521</pqid></control><display><type>article</type><title>Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment</title><source>Wiley Online Library Open Access</source><source>Wiley Online Library Journals Frontfile Complete</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Wang, Jie ; Huang, Qi ; He, Kun ; Li, Junpeng ; Guo, Tengfei ; Yang, Yang ; Lin, Zengping ; Li, Songye ; Vanderlinden, Greet ; Huang, Yiyun ; Van Laere, Koen ; Guan, Yihui ; Guo, Qihao ; Ni, Ruiqing ; Li, Binying ; Xie, Fang</creator><creatorcontrib>Wang, Jie ; Huang, Qi ; He, Kun ; Li, Junpeng ; Guo, Tengfei ; Yang, Yang ; Lin, Zengping ; Li, Songye ; Vanderlinden, Greet ; Huang, Yiyun ; Van Laere, Koen ; Guan, Yihui ; Guo, Qihao ; Ni, Ruiqing ; Li, Binying ; Xie, Fang</creatorcontrib><description>INTRODUCTION
Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD).
METHODS
Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT‐1 and [18F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition.
RESULTS
CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition.
CONCLUSIONS
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked.
Highlights
Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs.
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD.
Regional synaptic density was closely associated with regional mGluR5 availability.
mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition.
With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD.</description><identifier>ISSN: 1552-5260</identifier><identifier>ISSN: 1552-5279</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1002/alz.13817</identifier><identifier>PMID: 38634334</identifier><language>eng</language><publisher>United States: John Wiley and Sons Inc</publisher><subject>Alzheimer's disease ; amyloid deposition ; cognition ; mGluR5 availability ; PET/MR ; synaptic density</subject><ispartof>Alzheimer's & dementia, 2024-06, Vol.20 (6), p.3876-3888</ispartof><rights>2024 The Authors. published by Wiley Periodicals LLC on behalf of Alzheimer's Association.</rights><rights>2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4167-1267a28331eee44048fd7fa4a98acc2bebee735e5bdfd892c7f91f8a6114f6d63</citedby><cites>FETCH-LOGICAL-c4167-1267a28331eee44048fd7fa4a98acc2bebee735e5bdfd892c7f91f8a6114f6d63</cites><orcidid>0000-0003-2667-281X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180932/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180932/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38634334$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Jie</creatorcontrib><creatorcontrib>Huang, Qi</creatorcontrib><creatorcontrib>He, Kun</creatorcontrib><creatorcontrib>Li, Junpeng</creatorcontrib><creatorcontrib>Guo, Tengfei</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><creatorcontrib>Lin, Zengping</creatorcontrib><creatorcontrib>Li, Songye</creatorcontrib><creatorcontrib>Vanderlinden, Greet</creatorcontrib><creatorcontrib>Huang, Yiyun</creatorcontrib><creatorcontrib>Van Laere, Koen</creatorcontrib><creatorcontrib>Guan, Yihui</creatorcontrib><creatorcontrib>Guo, Qihao</creatorcontrib><creatorcontrib>Ni, Ruiqing</creatorcontrib><creatorcontrib>Li, Binying</creatorcontrib><creatorcontrib>Xie, Fang</creatorcontrib><title>Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment</title><title>Alzheimer's & dementia</title><addtitle>Alzheimers Dement</addtitle><description>INTRODUCTION
Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD).
METHODS
Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT‐1 and [18F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition.
RESULTS
CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition.
CONCLUSIONS
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked.
Highlights
Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs.
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD.
Regional synaptic density was closely associated with regional mGluR5 availability.
mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition.
With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD.</description><subject>Alzheimer's disease</subject><subject>amyloid deposition</subject><subject>cognition</subject><subject>mGluR5 availability</subject><subject>PET/MR</subject><subject>synaptic density</subject><issn>1552-5260</issn><issn>1552-5279</issn><issn>1552-5279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp1kctuEzEUhkcIREthwQsgL-kirW9zW6GoKlApEpUoLNhYZ-wziZFnPNhOquH5eDBc0kZ00Y2PLX_-fkt_Ubxl9IxRys_B_T5jomH1s-KYlSVflLxunx_2FT0qXsX4k1JJG1a-LI5EUwkphDwu_lwHjPMIU7KaGByjTXOeCcNgRzSkm8nX73xJri9viI1EOx_RzQRi9NpCysStTRsy-ZgOmgETdD4FP-XD2m0TDJkkATVOyQdSEtiBddBZd5cGoyF2NDhhXsZEfE9gmJ23hkyQNt759ZwBghBysvbr0Sa7Q2KHCWwY8pPXxYseXMQ39_Ok-Pbx8ubi82L15dPVxXK10JJV9YLxqgbeCMEQUUoqm97UPUhoG9Cad9gh1qLEsjO9aVqu675lfQMVY7KvTCVOig9777TtBjQ6Rwdwagp2gDArD1Y9vhntRq39TjHGGtoKng3v7w3B_9piTGqwUaNzMKLfRiWoZFywkrOMnu5RHXyMAftDDqPqrnaVa1f_as_su_8_diAfes7A-R64tQ7np01qufqxV_4Fz-y-1w</recordid><startdate>202406</startdate><enddate>202406</enddate><creator>Wang, Jie</creator><creator>Huang, Qi</creator><creator>He, Kun</creator><creator>Li, Junpeng</creator><creator>Guo, Tengfei</creator><creator>Yang, Yang</creator><creator>Lin, Zengping</creator><creator>Li, Songye</creator><creator>Vanderlinden, Greet</creator><creator>Huang, Yiyun</creator><creator>Van Laere, Koen</creator><creator>Guan, Yihui</creator><creator>Guo, Qihao</creator><creator>Ni, Ruiqing</creator><creator>Li, Binying</creator><creator>Xie, Fang</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2667-281X</orcidid></search><sort><creationdate>202406</creationdate><title>Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment</title><author>Wang, Jie ; Huang, Qi ; He, Kun ; Li, Junpeng ; Guo, Tengfei ; Yang, Yang ; Lin, Zengping ; Li, Songye ; Vanderlinden, Greet ; Huang, Yiyun ; Van Laere, Koen ; Guan, Yihui ; Guo, Qihao ; Ni, Ruiqing ; Li, Binying ; Xie, Fang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4167-1267a28331eee44048fd7fa4a98acc2bebee735e5bdfd892c7f91f8a6114f6d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Alzheimer's disease</topic><topic>amyloid deposition</topic><topic>cognition</topic><topic>mGluR5 availability</topic><topic>PET/MR</topic><topic>synaptic density</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Jie</creatorcontrib><creatorcontrib>Huang, Qi</creatorcontrib><creatorcontrib>He, Kun</creatorcontrib><creatorcontrib>Li, Junpeng</creatorcontrib><creatorcontrib>Guo, Tengfei</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><creatorcontrib>Lin, Zengping</creatorcontrib><creatorcontrib>Li, Songye</creatorcontrib><creatorcontrib>Vanderlinden, Greet</creatorcontrib><creatorcontrib>Huang, Yiyun</creatorcontrib><creatorcontrib>Van Laere, Koen</creatorcontrib><creatorcontrib>Guan, Yihui</creatorcontrib><creatorcontrib>Guo, Qihao</creatorcontrib><creatorcontrib>Ni, Ruiqing</creatorcontrib><creatorcontrib>Li, Binying</creatorcontrib><creatorcontrib>Xie, Fang</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alzheimer's & dementia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jie</au><au>Huang, Qi</au><au>He, Kun</au><au>Li, Junpeng</au><au>Guo, Tengfei</au><au>Yang, Yang</au><au>Lin, Zengping</au><au>Li, Songye</au><au>Vanderlinden, Greet</au><au>Huang, Yiyun</au><au>Van Laere, Koen</au><au>Guan, Yihui</au><au>Guo, Qihao</au><au>Ni, Ruiqing</au><au>Li, Binying</au><au>Xie, Fang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment</atitle><jtitle>Alzheimer's & dementia</jtitle><addtitle>Alzheimers Dement</addtitle><date>2024-06</date><risdate>2024</risdate><volume>20</volume><issue>6</issue><spage>3876</spage><epage>3888</epage><pages>3876-3888</pages><issn>1552-5260</issn><issn>1552-5279</issn><eissn>1552-5279</eissn><abstract>INTRODUCTION
Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD).
METHODS
Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT‐1 and [18F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition.
RESULTS
CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition.
CONCLUSIONS
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked.
Highlights
Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs.
Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD.
Regional synaptic density was closely associated with regional mGluR5 availability.
mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition.
With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD.</abstract><cop>United States</cop><pub>John Wiley and Sons Inc</pub><pmid>38634334</pmid><doi>10.1002/alz.13817</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-2667-281X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Open Access; Wiley Online Library Journals Frontfile Complete; PubMed Central; PubMed Central Open Access |
| subjects | Alzheimer's disease amyloid deposition cognition mGluR5 availability PET/MR synaptic density |
| title | Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment |
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