Multi-omic Characterization of Brain Changes in the Vascular Endothelial Growth Factor Family During Aging and Alzheimer's Disease

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2023 Mar 11

PMID 36905877

Authors

Mabel Seto

Logan Dumitrescu

Emily R Mahoney

Annah M Sclafani

Philip L De Jager

Vilas Menon

Mary E I Koran

Rena A Robinson

Douglas M Ruderfer

Nancy J Cox

Nicholas T Seyfried

Angela L Jefferson

Julie A Schneider

David A Bennett

Vladislav A Petyuk

Timothy J Hohman

Affiliations

Soon will be listed here.

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.

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