White matter hyperintensity volume modifies the association between CSF vascular inflammatory biomarkers and regional FDG-PET along the Alzheimer's disease continuum

Neurobiol Aging. 2023 Dec:132:1-12. doi: 10.1016/j.neurobiolaging.2023.08.002. Epub 2023 Aug 10.

Abstract

In older adults with abnormal levels of Alzheimer's disease neuropathology, lower cerebrospinal fluid (CSF) vascular endothelial growth factor (VEGF) levels are associated with lower [¹⁸F]-fluorodeoxyglucose positron emission tomography (FDG-PET) signal, but whether this association is (1) specific to VEGF or broadly driven by vascular inflammation, or (2) modified by vascular risk (e.g., white matter hyperintensities [WMHs]) remains unknown. To address this and build upon our past work, we evaluated whether 5 CSF vascular inflammation biomarkers (vascular cell adhesion molecule 1, VEGF, C-reactive protein, fibrinogen, and von Willebrand factor)-previously associated with CSF amyloid levels-were related to FDG-PET signal and whether WMH volume modified these associations in 158 Alzheimer's Disease Neuroimaging Initiative participants (55-90 years old, 39 cognitively normal, 80 mild cognitive impairment, 39 Alzheimer's disease). We defined regions both by cortical boundary and by the 3 major vascular territories: anterior, middle, and posterior cerebral arteries. We found that WMH volume had interactive effects with CSF biomarkers (VEGF and C-reactive protein) on FDG-PET throughout the cortex in both vascular territories and conventionally defined regions of interest.

Keywords: CRP; Glucose metabolism; VEGF; Vascular territories; White matter hyperintensities.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism
  • C-Reactive Protein
  • Cognitive Dysfunction* / metabolism
  • Fluorodeoxyglucose F18 / metabolism
  • Humans
  • Inflammation / metabolism
  • Magnetic Resonance Imaging
  • Positron-Emission Tomography / methods
  • Vascular Endothelial Growth Factor A / metabolism
  • White Matter* / pathology

Substances

  • Fluorodeoxyglucose F18
  • Vascular Endothelial Growth Factor A
  • C-Reactive Protein
  • Biomarkers
  • Amyloid beta-Peptides