Regional relationships between CSF VEGF levels and Alzheimer's disease brain biomarkers and cognition
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)
Neurobiology of aging
Digital Object Identifier (DOI)
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.