{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Seto M"],"funding":["NICHD NIH HHS","NCATS NIH HHS","NIA NIH HHS","NINDS NIH HHS","NIH HHS"],"pagination":["25-33"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10106439"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["126"],"pubmed_abstract":["The vascular endothelial growth factor (VEGF) signaling family has been implicated in neuroprotection and clinical progression in Alzheimer's disease (AD). Previous work in postmortem human dorsolateral prefrontal cortex demonstrated that higher transcript levels of VEGFB, PGF, FLT1, and FLT4 are associated with AD dementia, worse cognitive outcomes, and higher AD neuropathology. To expand prior work, we leveraged bulk RNA sequencing data, single nucleus RNA (snRNA) sequencing, and both tandem mass tag and selected reaction monitoring mass spectrometry proteomic measures from the post-mortem brain. Outcomes included AD diagnosis, cognition, and AD neuropathology. We replicated previously reported VEGFB and FLT1 results, whereby higher expression was associated with worse outcomes, and snRNA results suggest microglia, oligodendrocytes, and endothelia may play a central role in these associations. Additionally, FLT4 and NRP2 expression were associated with better cognitive outcomes. This study provides a comprehensive molecular picture of the VEGF signaling family in cognitive aging and AD and critical insight towards the biomarker and therapeutic potential of VEGF family members in AD."],"journal":["Neurobiology of aging"],"pubmed_title":["Multi-omic characterization of brain changes in the vascular endothelial growth factor family during aging and Alzheimer's disease."],"pmcid":["PMC10106439"],"funding_grant_id":["U01 AG061356","R01 AG015819","R01 AG061518","K12 HD043483","R01 AG059716","R01 AG036836","U01 AG046152","R21 AG059941","R01 AG030146","R01 AG056534","K24 AG046373","K01 AG049164","RF1 AG057473","P30 AG010161","UL1 TR000445","R01 NS100980","R01 AG034962","R01 AG036042","P20 AG068082","U01 AG046161","RC2 AG036547","P30 AG066511","S10 OD023680","R01 AG048015","U01 AG032984","R01 AG017917"],"pubmed_authors":["Dumitrescu L","Jefferson AL","Robinson RA","Mahoney ER","Sclafani AM","Hohman TJ","Menon V","Seyfried NT","Petyuk VA","Schneider JA","Bennett DA","Koran MEI","Cox NJ","Ruderfer DM","Seto M","De Jager PL"],"additional_accession":[]},"is_claimable":false,"name":"Multi-omic characterization of brain changes in the vascular endothelial growth factor family during aging and Alzheimer's disease.","description":"The vascular endothelial growth factor (VEGF) signaling family has been implicated in neuroprotection and clinical progression in Alzheimer's disease (AD). Previous work in postmortem human dorsolateral prefrontal cortex demonstrated that higher transcript levels of VEGFB, PGF, FLT1, and FLT4 are associated with AD dementia, worse cognitive outcomes, and higher AD neuropathology. To expand prior work, we leveraged bulk RNA sequencing data, single nucleus RNA (snRNA) sequencing, and both tandem mass tag and selected reaction monitoring mass spectrometry proteomic measures from the post-mortem brain. Outcomes included AD diagnosis, cognition, and AD neuropathology. We replicated previously reported VEGFB and FLT1 results, whereby higher expression was associated with worse outcomes, and snRNA results suggest microglia, oligodendrocytes, and endothelia may play a central role in these associations. Additionally, FLT4 and NRP2 expression were associated with better cognitive outcomes. This study provides a comprehensive molecular picture of the VEGF signaling family in cognitive aging and AD and critical insight towards the biomarker and therapeutic potential of VEGF family members in AD.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jun","modification":"2024-11-13T04:02:45.557Z","creation":"2024-11-13T04:02:45.557Z"},"accession":"S-EPMC10106439","cross_references":{"pubmed":["36905877"],"doi":["10.1016/j.neurobiolaging.2023.01.010"]}}