Regional relationships between CSF VEGF levels and Alzheimer's disease brain biomarkers and cognition

Authors

Meral A. Tubi, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Deydeep Kothapalli, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Matthew Hapenney, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Franklin W. Feingold, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA; Stanford University, Stanford, CA 94305.
Wendy J. Mack, Division of Biostatistics, Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
Kevin S. King, Huntington Medical Research Institutes, Imaging Division, Pasadena, CA, 91105 USA.
Paul M. Thompson, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Meredith N. Braskie, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA. Electronic address: braskie@usc.edu.

Document Type

Article

Abstract

Vascular endothelial growth factor (VEGF) is a complex signaling protein that supports vascular and neuronal function. Alzheimer's disease (AD) -neuropathological hallmarks interfere with VEGF signaling and modify previously detected positive associations between cerebral spinal fluid (CSF) VEGF and cognition and hippocampal volume. However, it remains unknown 1) whether regional relationships between VEGF and glucose metabolism and cortical thinning exist, and 2) whether AD-neuropathological hallmarks (CSF Aβ, t-tau, p-tau) also modify these relationships. We addressed this in 310 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (92 cognitively normal, 149 mild cognitive impairment, 69 AD; 215 CSF Aβ+, 95 CSF Aβ-) with regional cortical thickness and cognition measurements and 158 participants with FDG-PET. In Aβ + participants (CSF Aβ ≤ 192 pg/mL), higher CSF VEGF levels were associated with greater FDG-PET signal in the inferior parietal, and middle and inferior temporal cortices. Abnormal CSF amyloid and tau levels strengthened the positive association between VEGF and regional FDG-PET indices. VEGF also had both direct associations with semantic memory, as well as indirect associations mediated by regional FDG-PET signal to cognition.

Medical Subject Headings

Aged; Aged, 80 and over; Alzheimer Disease (diagnosis, pathology, psychology); Amyloid beta-Peptides (cerebrospinal fluid); Biomarkers (cerebrospinal fluid); Cerebral Cortex (pathology); Cognition; Executive Function; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Vascular Endothelial Growth Factor A (cerebrospinal fluid); tau Proteins (cerebrospinal fluid)

Publication Date

9-1-2021

Publication Title

Neurobiology of aging

E-ISSN

1558-1497

Volume

105

First Page

241

Last Page

251

PubMed ID

34126466

Digital Object Identifier (DOI)

10.1016/j.neurobiolaging.2021.04.025

Recommended Citation

Tubi, Meral A.; Kothapalli, Deydeep; Hapenney, Matthew; Feingold, Franklin W.; Mack, Wendy J.; King, Kevin S.; Thompson, Paul M.; and Braskie, Meredith N., "Regional relationships between CSF VEGF levels and Alzheimer's disease brain biomarkers and cognition" (2021). Neuroradiology. 59.
https://scholar.barrowneuro.org/neuroradiology/59