Omics‐derived biological modules reflect metabolic brain changes in Alzheimer's disease
INTRODUCTION Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive. METHODS Here, w...
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| creator | Povala, Guilherme De Bastiani, Marco Antônio Bellaver, Bruna Ferreira, Pamela C. L. Ferrari‐Souza, João Pedro Lussier, Firoza Z. Souza, Diogo O. Rosa‐Neto, Pedro Pascoal, Tharick A. Zatt, Bruno Zimmer, Eduardo R. |
| description | INTRODUCTION
Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive.
METHODS
Here, we integrated [18F]FDG‐PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel‐wise linear regression analysis.
RESULTS
Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG‐PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak‐t(223) = 4.86, P value |
| doi_str_mv | 10.1002/alz.14095 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11485394</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3092870357</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3765-8883ef23664aa4baecbb02eecd47a74f27b6cf45255c1ed2977aba2faa13d2f13</originalsourceid><addsrcrecordid>eNp1kUtOHDEQhi2UiPeCC0S9CywG_Gx3r9AIkYc0EhtYwMYqu6tnjNxtYs-AYJUj5Iw5SZwMGYVFVlVSffqqVD8hR4yeMkr5GYSXUyZpq7bILlOKTxTX7btNX9MdspfzPaWSNkxtkx3RFlzUbJfcXg3e5Z_ff3SY_CN2lfUxxLl3EKohdquAuUrYB3TLasAl2Bi8q2wCP1ZuAeO8zEs7DS8L9AOmj7nqfEbIeEDe9xAyHr7WfXLz6fL64stkdvX568V0NnFC12rSNI3Anou6lgDSAjprKUd0ndSgZc-1rV0vFVfKMex4qzVY4D0AEx3vmdgn52vvw8oO2DkclwmCeUh-gPRsInjzdjL6hZnHR8OYbJRoZTEcvxpS_LbCvDSDzw5DgBHjKhtBW95oKpQu6MkadSnmXB6z2cOo-Z2FKVmYP1kU9sO_h23Iv88vwNkaePIBn_9vMtPZ3Vr5Cx0Ilv0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3092870357</pqid></control><display><type>article</type><title>Omics‐derived biological modules reflect metabolic brain changes in Alzheimer's disease</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>Povala, Guilherme ; De Bastiani, Marco Antônio ; Bellaver, Bruna ; Ferreira, Pamela C. L. ; Ferrari‐Souza, João Pedro ; Lussier, Firoza Z. ; Souza, Diogo O. ; Rosa‐Neto, Pedro ; Pascoal, Tharick A. ; Zatt, Bruno ; Zimmer, Eduardo R.</creator><creatorcontrib>Povala, Guilherme ; De Bastiani, Marco Antônio ; Bellaver, Bruna ; Ferreira, Pamela C. L. ; Ferrari‐Souza, João Pedro ; Lussier, Firoza Z. ; Souza, Diogo O. ; Rosa‐Neto, Pedro ; Pascoal, Tharick A. ; Zatt, Bruno ; Zimmer, Eduardo R. ; Alzheimer's Disease Neuroimaging Initiative ; for the Alzheimer's Disease Neuroimaging Initiative</creatorcontrib><description>INTRODUCTION
Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive.
METHODS
Here, we integrated [18F]FDG‐PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel‐wise linear regression analysis.
RESULTS
Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG‐PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak‐t(223) = 4.86, P value < 0.001) and zinc‐finger–related regulatory units (peak‐t(223) = 3.90, P value < 0.001).
DISCUSSION
By integrating transcriptomics with PET imaging data, we identified that serine/threonine kinase activity–associated genes and zinc‐finger–related regulatory units are highly associated with brain metabolic changes in AD.
Highlights
We conducted an integrated analysis of system‐based transcriptomics and fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) at the voxel level in Alzheimer's disease (AD).
The biological process of serine/threonine kinase activity was the most associated with [18F]FDG‐PET in the AD brain.
Serine/threonine kinase activity alterations are associated with brain vulnerable regions in AD [18F]FDG‐PET.
Zinc‐finger transcription factor targets were associated with AD brain [18F]FDG‐PET metabolism.</description><identifier>ISSN: 1552-5260</identifier><identifier>ISSN: 1552-5279</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1002/alz.14095</identifier><identifier>PMID: 39140361</identifier><language>eng</language><publisher>United States: John Wiley and Sons Inc</publisher><subject>Alzheimer's disease ; fluorodeoxyglucose positron emission tomography ; systems biology ; transcriptomics</subject><ispartof>Alzheimer's & dementia, 2024-10, Vol.20 (10), p.6709-6721</ispartof><rights>2024 The Author(s). published by Wiley Periodicals LLC on behalf of Alzheimer's Association.</rights><rights>2024 The Author(s). 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><cites>FETCH-LOGICAL-c3765-8883ef23664aa4baecbb02eecd47a74f27b6cf45255c1ed2977aba2faa13d2f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485394/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485394/$$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/39140361$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Povala, Guilherme</creatorcontrib><creatorcontrib>De Bastiani, Marco Antônio</creatorcontrib><creatorcontrib>Bellaver, Bruna</creatorcontrib><creatorcontrib>Ferreira, Pamela C. L.</creatorcontrib><creatorcontrib>Ferrari‐Souza, João Pedro</creatorcontrib><creatorcontrib>Lussier, Firoza Z.</creatorcontrib><creatorcontrib>Souza, Diogo O.</creatorcontrib><creatorcontrib>Rosa‐Neto, Pedro</creatorcontrib><creatorcontrib>Pascoal, Tharick A.</creatorcontrib><creatorcontrib>Zatt, Bruno</creatorcontrib><creatorcontrib>Zimmer, Eduardo R.</creatorcontrib><creatorcontrib>Alzheimer's Disease Neuroimaging Initiative</creatorcontrib><creatorcontrib>for the Alzheimer's Disease Neuroimaging Initiative</creatorcontrib><title>Omics‐derived biological modules reflect metabolic brain changes in Alzheimer's disease</title><title>Alzheimer's & dementia</title><addtitle>Alzheimers Dement</addtitle><description>INTRODUCTION
Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive.
METHODS
Here, we integrated [18F]FDG‐PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel‐wise linear regression analysis.
RESULTS
Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG‐PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak‐t(223) = 4.86, P value < 0.001) and zinc‐finger–related regulatory units (peak‐t(223) = 3.90, P value < 0.001).
DISCUSSION
By integrating transcriptomics with PET imaging data, we identified that serine/threonine kinase activity–associated genes and zinc‐finger–related regulatory units are highly associated with brain metabolic changes in AD.
Highlights
We conducted an integrated analysis of system‐based transcriptomics and fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) at the voxel level in Alzheimer's disease (AD).
The biological process of serine/threonine kinase activity was the most associated with [18F]FDG‐PET in the AD brain.
Serine/threonine kinase activity alterations are associated with brain vulnerable regions in AD [18F]FDG‐PET.
Zinc‐finger transcription factor targets were associated with AD brain [18F]FDG‐PET metabolism.</description><subject>Alzheimer's disease</subject><subject>fluorodeoxyglucose positron emission tomography</subject><subject>systems biology</subject><subject>transcriptomics</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>eNp1kUtOHDEQhi2UiPeCC0S9CywG_Gx3r9AIkYc0EhtYwMYqu6tnjNxtYs-AYJUj5Iw5SZwMGYVFVlVSffqqVD8hR4yeMkr5GYSXUyZpq7bILlOKTxTX7btNX9MdspfzPaWSNkxtkx3RFlzUbJfcXg3e5Z_ff3SY_CN2lfUxxLl3EKohdquAuUrYB3TLasAl2Bi8q2wCP1ZuAeO8zEs7DS8L9AOmj7nqfEbIeEDe9xAyHr7WfXLz6fL64stkdvX568V0NnFC12rSNI3Anou6lgDSAjprKUd0ndSgZc-1rV0vFVfKMex4qzVY4D0AEx3vmdgn52vvw8oO2DkclwmCeUh-gPRsInjzdjL6hZnHR8OYbJRoZTEcvxpS_LbCvDSDzw5DgBHjKhtBW95oKpQu6MkadSnmXB6z2cOo-Z2FKVmYP1kU9sO_h23Iv88vwNkaePIBn_9vMtPZ3Vr5Cx0Ilv0</recordid><startdate>202410</startdate><enddate>202410</enddate><creator>Povala, Guilherme</creator><creator>De Bastiani, Marco Antônio</creator><creator>Bellaver, Bruna</creator><creator>Ferreira, Pamela C. L.</creator><creator>Ferrari‐Souza, João Pedro</creator><creator>Lussier, Firoza Z.</creator><creator>Souza, Diogo O.</creator><creator>Rosa‐Neto, Pedro</creator><creator>Pascoal, Tharick A.</creator><creator>Zatt, Bruno</creator><creator>Zimmer, Eduardo R.</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></search><sort><creationdate>202410</creationdate><title>Omics‐derived biological modules reflect metabolic brain changes in Alzheimer's disease</title><author>Povala, Guilherme ; De Bastiani, Marco Antônio ; Bellaver, Bruna ; Ferreira, Pamela C. L. ; Ferrari‐Souza, João Pedro ; Lussier, Firoza Z. ; Souza, Diogo O. ; Rosa‐Neto, Pedro ; Pascoal, Tharick A. ; Zatt, Bruno ; Zimmer, Eduardo R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3765-8883ef23664aa4baecbb02eecd47a74f27b6cf45255c1ed2977aba2faa13d2f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Alzheimer's disease</topic><topic>fluorodeoxyglucose positron emission tomography</topic><topic>systems biology</topic><topic>transcriptomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Povala, Guilherme</creatorcontrib><creatorcontrib>De Bastiani, Marco Antônio</creatorcontrib><creatorcontrib>Bellaver, Bruna</creatorcontrib><creatorcontrib>Ferreira, Pamela C. L.</creatorcontrib><creatorcontrib>Ferrari‐Souza, João Pedro</creatorcontrib><creatorcontrib>Lussier, Firoza Z.</creatorcontrib><creatorcontrib>Souza, Diogo O.</creatorcontrib><creatorcontrib>Rosa‐Neto, Pedro</creatorcontrib><creatorcontrib>Pascoal, Tharick A.</creatorcontrib><creatorcontrib>Zatt, Bruno</creatorcontrib><creatorcontrib>Zimmer, Eduardo R.</creatorcontrib><creatorcontrib>Alzheimer's Disease Neuroimaging Initiative</creatorcontrib><creatorcontrib>for the Alzheimer's Disease Neuroimaging Initiative</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>Povala, Guilherme</au><au>De Bastiani, Marco Antônio</au><au>Bellaver, Bruna</au><au>Ferreira, Pamela C. L.</au><au>Ferrari‐Souza, João Pedro</au><au>Lussier, Firoza Z.</au><au>Souza, Diogo O.</au><au>Rosa‐Neto, Pedro</au><au>Pascoal, Tharick A.</au><au>Zatt, Bruno</au><au>Zimmer, Eduardo R.</au><aucorp>Alzheimer's Disease Neuroimaging Initiative</aucorp><aucorp>for the Alzheimer's Disease Neuroimaging Initiative</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Omics‐derived biological modules reflect metabolic brain changes in Alzheimer's disease</atitle><jtitle>Alzheimer's & dementia</jtitle><addtitle>Alzheimers Dement</addtitle><date>2024-10</date><risdate>2024</risdate><volume>20</volume><issue>10</issue><spage>6709</spage><epage>6721</epage><pages>6709-6721</pages><issn>1552-5260</issn><issn>1552-5279</issn><eissn>1552-5279</eissn><abstract>INTRODUCTION
Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive.
METHODS
Here, we integrated [18F]FDG‐PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel‐wise linear regression analysis.
RESULTS
Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG‐PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak‐t(223) = 4.86, P value < 0.001) and zinc‐finger–related regulatory units (peak‐t(223) = 3.90, P value < 0.001).
DISCUSSION
By integrating transcriptomics with PET imaging data, we identified that serine/threonine kinase activity–associated genes and zinc‐finger–related regulatory units are highly associated with brain metabolic changes in AD.
Highlights
We conducted an integrated analysis of system‐based transcriptomics and fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) at the voxel level in Alzheimer's disease (AD).
The biological process of serine/threonine kinase activity was the most associated with [18F]FDG‐PET in the AD brain.
Serine/threonine kinase activity alterations are associated with brain vulnerable regions in AD [18F]FDG‐PET.
Zinc‐finger transcription factor targets were associated with AD brain [18F]FDG‐PET metabolism.</abstract><cop>United States</cop><pub>John Wiley and Sons Inc</pub><pmid>39140361</pmid><doi>10.1002/alz.14095</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alzheimer's disease fluorodeoxyglucose positron emission tomography systems biology transcriptomics |
| title | Omics‐derived biological modules reflect metabolic brain changes in Alzheimer's disease |
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