Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 25-33 |
| Number of pages | 9 |
| Journal | Neurobiology of Aging |
| Volume | 126 |
| DOIs | |
| Publication status | Published - 1 Jun 2023 |
| Externally published | Yes |
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Multi-omic characterization of brain changes in the vascular endothelial growth factor family during aging and Alzheimer's disease. / Seto, Mabel; Dumitrescu, Logan; Mahoney, Emily R. et al.
In: Neurobiology of Aging, Vol. 126, 01.06.2023, p. 25-33.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Multi-omic characterization of brain changes in the vascular endothelial growth factor family during aging and Alzheimer's disease
AU - Seto, Mabel
AU - Dumitrescu, Logan
AU - Mahoney, Emily R.
AU - Sclafani, Annah M.
AU - de Jager, Philip L.
AU - Menon, Vilas
AU - Koran, Mary E. I.
AU - Robinson, Renã A.
AU - Ruderfer, Douglas M.
AU - Cox, Nancy J.
AU - Seyfried, Nicholas T.
AU - Jefferson, Angela L.
AU - Schneider, Julie A.
AU - Bennett, David A.
AU - Petyuk, Vladislav A.
AU - Hohman, Timothy J.
N1 - Funding Information: The results published here are in whole or in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.synapse.org). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161 (ROS), R01AG15819 (ROSMAP; genomics and RNAseq), R01AG17917 (MAP), R01AG30146, R01AG36042 (5hC methylation, ATACseq), RC2AG036547 (H3K9Ac), R01AG36836 (RNAseq), R01AG48015 (monocyte RNAseq) RF1AG57473 (single nucleus RNAseq), U01AG32984 (genomic and whole exome sequencing), U01AG46152 (ROSMAP AMP-AD, targeted proteomics), U01AG46161(TMT proteomics), U01AG61356 (whole genome sequencing, targeted proteomics, ROSMAP AMP-AD), the Illinois Department of Public Health (ROSMAP), and the Translational Genomics Research Institute (genomic). Additional phenotypic data can be requested at www.radc.rush.edu. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the validation analyses described in this manuscript were obtained from dbGaP accession number phs000424.GTEx.v8.p2 on 11/13/2019. Additional support includes K01-AG049164, R01-AG059716, R01-AG061518, R21-AG05994, K12-HD043483, K24-AG046373, HHSN311201600276P, S10-OD023680, R01-AG034962, R01-NS100980, R01-AG056534, P30-AG010161, R01-AG15819, R01-AG17917, U01-AG46152, Vanderbilt Clinical Translational Science Award (UL1-TR000445), the Vanderbilt Memory and Alzheimer's Center, and the Vanderbilt Alzheimer's Disease Research Center (P20-AGAG068082). Funding Information: The results published here are in whole or in part based on data obtained from the AD Knowledge Portal ( https://adknowledgeportal.synapse.org ). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161 (ROS), R01AG15819 (ROSMAP; genomics and RNAseq), R01AG17917 (MAP), R01AG30146, R01AG36042 (5hC methylation, ATACseq), RC2AG036547 (H3K9Ac), R01AG36836 (RNAseq), R01AG48015 (monocyte RNAseq) RF1AG57473 (single nucleus RNAseq), U01AG32984 (genomic and whole exome sequencing), U01AG46152 (ROSMAP AMP-AD, targeted proteomics), U01AG46161(TMT proteomics), U01AG61356 (whole genome sequencing, targeted proteomics, ROSMAP AMP-AD), the Illinois Department of Public Health (ROSMAP), and the Translational Genomics Research Institute (genomic). Additional phenotypic data can be requested at www.radc.rush.edu . The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the validation analyses described in this manuscript were obtained from dbGaP accession number phs000424.GTEx.v8.p2 on 11/13/2019. Additional support includes K01-AG049164, R01-AG059716, R01-AG061518, R21-AG05994, K12-HD043483, K24-AG046373, HHSN311201600276P, S10-OD023680, R01-AG034962, R01-NS100980, R01-AG056534, P30-AG010161, R01-AG15819, R01-AG17917, U01-AG46152, Vanderbilt Clinical Translational Science Award (UL1-TR000445), the Vanderbilt Memory and Alzheimer's Center, and the Vanderbilt Alzheimer's Disease Research Center (P20-AGAG068082). Publisher Copyright: © 2023 The Authors
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Cognition
KW - Proteomics
KW - Transcriptomics
KW - VEGF
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85150778446&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36905877
U2 - 10.1016/j.neurobiolaging.2023.01.010
DO - 10.1016/j.neurobiolaging.2023.01.010
M3 - Article
C2 - 36905877
SN - 0197-4580
VL - 126
SP - 25
EP - 33
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -